[ { "key": "H9WMXMA2", "version": 12, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/H9WMXMA2", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/H9WMXMA2", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/JFMF4RCS", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "H9WMXMA2", "version": 12, "parentItem": "JFMF4RCS", "itemType": "attachment", "linkMode": "linked_url", "title": "Snapshot", "accessDate": "2013-04-16T18:45:01Z", "url": "http://onlinelibrary.wiley.com/doi/10.1002/poc.1679/abstract", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-16T18:45:01Z", "dateModified": "2013-04-16T18:45:01Z" } }, { "key": "JFMF4RCS", "version": 12, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/JFMF4RCS", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/JFMF4RCS", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Abroshan et al.", "parsedDate": "2010", "numChildren": 2 }, "data": { "key": "JFMF4RCS", "version": 12, "itemType": "journalArticle", "title": "Molecular dynamics simulation and MM–PBSA calculations of sickle cell hemoglobin in dimer form with Val, Trp, or Phe at the lateral contact", "creators": [ { "creatorType": "author", "firstName": "Hadi", "lastName": "Abroshan" }, { "creatorType": "author", "firstName": "Hamed", "lastName": "Akbarzadeh" }, { "creatorType": "author", "firstName": "Golam Abbas", "lastName": "Parsafar" } ], "abstractNote": "As the delay time and hence nuclei formation play a crucial role in the pathophysiology of sickle cell disease, MD simulation and molecular mechanics–Poisson–Boltzmann surface area (MM–PBSA) calculations have been performed on three systems of hemoglobin; namely dimer of hemoglobin with valine (Hb S), tryptophan (Hbβ6W), and phenylalanine (Hbβ6F) at β6 position. The structural changes due to these aromatic substitutions are investigated. It is shown that β subunits have significant impact on the differences between a dimer and other crystal structures. Transition from a dimer to polymer for Hb S system affects the donor molecule more than that of the acceptor. In the case of donor and acceptor subunits, the RMSD values are ordered as Hbβ6F > Hbβ6W > Hb S which predicts a larger deviation for the Hbβ6F dimer. It is shown that the formation of stable dimers is in the order of Hbβ6F > Hb S > Hbβ6W, but contribution of the β6 residue in Hbβ6W is more than two other systems. This study shows that the interaction of β6 residue in Hb S is mostly van der Waals type, but in two other systems the electrostatic interaction is also noticeable, especially in the case of Hbβ6W in which the hydrogen bond plays an important role in the association of monomers. Trp and Phe also have a stabilizing van der Waals interaction with a hydrophobic pocket composed of 1β2-10Ala, 1β2-125Pro, 1β2-126Val, and 1β2-129Ala. Our survey shows that the role of 2β1-85Phe is very important only in the nucleus formation of Hb S, but not for the subsequent processes. Copyright © 2010 John Wiley & Sons, Ltd.", "publicationTitle": "Journal of Physical Organic Chemistry", "publisher": "", "place": "", "date": "2010", "volume": "23", "issue": "9", "section": "", "partNumber": "", "partTitle": "", "pages": "866–877", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1002/poc.1679", "citationKey": "", "url": "http://onlinelibrary.wiley.com/doi/10.1002/poc.1679/abstract", "accessDate": "2013-04-16T18:45:01Z", "PMID": "", "PMCID": "", "ISSN": "1099-1395", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "Wiley Online Library", "callNumber": "", "rights": "Copyright © 2010 John Wiley & Sons, Ltd.", "extra": "", "tags": [ { "tag": "molecular disease", "type": 1 }, { "tag": "molecular dynamics simulation", "type": 1 }, { "tag": "protein polymerization", "type": 1 }, { "tag": "protein–protein interaction", "type": 1 }, { "tag": "sickle cell hemoglobin", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2013-04-16T18:45:01Z", "dateModified": "2013-04-16T18:45:01Z" } }, { "key": "XKS5RIFF", "version": 12, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/XKS5RIFF", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/XKS5RIFF", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/JFMF4RCS", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "XKS5RIFF", "version": 12, "parentItem": "JFMF4RCS", "itemType": "attachment", "linkMode": "linked_url", "title": "Full Text PDF", "accessDate": "2013-04-16T18:45:01Z", "url": "http://onlinelibrary.wiley.com/store/10.1002/poc.1679/asset/1679_ftp.pdf?v=1&t=hflf8ez9&s=ccf449d57e2e47fa5c36fd9a9efb67d090a227f8", "note": "", "contentType": "application/pdf", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-16T18:45:01Z", "dateModified": "2013-04-16T18:45:01Z" } }, { "key": "D67DZZTU", "version": 11, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/D67DZZTU", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/D67DZZTU", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/7N8T8QVX", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "D67DZZTU", "version": 11, "parentItem": "7N8T8QVX", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed Central Link", "accessDate": "2013-04-16T00:34:49Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC333223/", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-16T00:34:49Z", "dateModified": "2013-04-16T00:34:49Z" } }, { "key": "7N8T8QVX", "version": 11, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/7N8T8QVX", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/7N8T8QVX", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Deiderich et al.", "parsedDate": "1976-09", "numChildren": 1 }, "data": { "key": "7N8T8QVX", "version": 11, "itemType": "journalArticle", "title": "Hematologic and clinical responses in patients with sickle cell anemia after chronic extracorporeal red cell carbamylation.", "creators": [ { "creatorType": "author", "firstName": "D A", "lastName": "Deiderich" }, { "creatorType": "author", "firstName": "R C", "lastName": "Trueworthy" }, { "creatorType": "author", "firstName": "P", "lastName": "Gill" }, { "creatorType": "author", "firstName": "A M", "lastName": "Cader" }, { "creatorType": "author", "firstName": "W E", "lastName": "Larsen" } ], "abstractNote": "In eight patients with sickle cell anemia, weekly extracorporeal carbamylation of about 20% of the circulating red cell mass was carried out for 2 yr or longer. At each visit, a mean of 1.3+/-0.2 mol of cyanate were incorporated per mole of hemoglobin in the carbamylated erythrocytes. Within 3 mo, a stable level of about 35-50% of the circulating erythrocytes was carbamylated. This quantity and degree of hemoglobin carbamylation produced a decrease in mean whole blood P50 from 33 to 26 mm Hg. During the first 3 mo of carbamylation, the mean hemoglobin increased from 6.4 to 9.1 g/100 ml, while mean absolute reticulocytes decreased by 58% and circulating irreversibly sickled erythrocytes decreased by 65%. The mean red cell life span increased from 13 days before treatment to 21.6 days after 3 mo of carbamylation. Beyond the 3rd mo of carbamylation, blood P50, hemoglobin, and reticulocytes remained quite stable. No toxic effects of extracorporeal carbamylation of erythrocytes were noted. The capacity of blood to release oxygen at 30 mm Hg PO2 increased from 4.3 to 5.0 cm3/100 ml blood during carbamylation. The overall frequency of severe painful crises decreased by about 80% during carbamylation. Before carbamylation, 34% of the crises were induced by a concomitant illness, usually an infection. During carbamylation, the incidence of induced crises decreased 50% while spontaneous crises virtually disappeared. The marked improvements in hematologic parameters and the decreased frequency of severe painful crises observed during this study offer sufficient promise to warrant further exploration, hopefully using more efficient techniques, of the clinical efficacy of extracorporeal erythrocyte carbamylation in sickle cell anemia.", "publicationTitle": "Journal of Clinical Investigation", "publisher": "", "place": "", "date": "1976-9", "volume": "58", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "642-653", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Clin Invest", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC333223/", "accessDate": "2013-04-16T00:34:49Z", "PMID": "", "PMCID": "", "ISSN": "0021-9738", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 956392\nPMCID: PMC333223", "tags": [], "collections": [], "relations": {}, "dateAdded": "2013-04-16T00:34:49Z", "dateModified": "2013-04-16T00:34:49Z" } }, { "key": "X3HAJZM3", "version": 10, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/X3HAJZM3", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/X3HAJZM3", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/AERDVQCJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "X3HAJZM3", "version": 10, "parentItem": "AERDVQCJ", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-04-15T19:50:41Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/8663330", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-15T19:50:41Z", "dateModified": "2013-04-15T19:50:41Z" } }, { "key": "AERDVQCJ", "version": 10, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/AERDVQCJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/AERDVQCJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Lesecq et al.", "parsedDate": "1996-07-19", "numChildren": 1 }, "data": { "key": "AERDVQCJ", "version": 10, "itemType": "journalArticle", "title": "Functional studies and polymerization of recombinant hemoglobin Glu-alpha2beta26(A3) --> Val/Glu-7(A4) --> Ala", "creators": [ { "creatorType": "author", "firstName": "S", "lastName": "Lesecq" }, { "creatorType": "author", "firstName": "V", "lastName": "Baudin" }, { "creatorType": "author", "firstName": "J", "lastName": "Kister" }, { "creatorType": "author", "firstName": "M C", "lastName": "Marden" }, { "creatorType": "author", "firstName": "C", "lastName": "Poyart" }, { "creatorType": "author", "firstName": "J", "lastName": "Pagnier" } ], "abstractNote": "In hemoglobin (Hb) S the hydrophobic mutated residue Val-beta6(A3) (donor site) closely interacts with the hydrophobic side groups of Phe-beta85(F1) and Leu-beta88(F4) (EF pocket, acceptor site) of a neighboring tetramer, resulting in decreased solubility and polymerization of the deoxy-Hb. The beta6(A3) residue is followed by two charged residues Glu-beta7(A4) and Lys-beta8(A5). This cluster has no attraction for the hydrophobic EF pocket. We have modified the beta7(A4) residue next to the donor site Val-beta6(A3), replacing the charged Glu by a hydrophobic Ala-(rHb betaE6V/E7A). The single mutant Glu-beta7 --> Ala-(rHb betaE7A) was also engineered. Both rHbs exhibit a heat instability and an increased oxygen affinity compared to Hb A and Hb S. There was a concentration dependence of the ligand binding properties (1-300 microM in heme) indicating an increased amount of dimers relative to Hb A. The deoxy form of rHb betaE6V/E7A polymerizes in vitro, with a decreased rate of polymer formation relative to Hb S, while the single mutant betaE7A does not polymerize in the same experimental conditions. The Glu-beta7(A4) --> Ala substitution does not increase the hydrophobic interaction between donor and acceptor site. We speculate that the loss of the normal saline bridge between Glu-beta7(A4) and Lys-beta132(H10) leads to an increased flexibility of the A helix and may account for the difference of the polymerization for this Hb S mutant.", "publicationTitle": "The Journal of biological chemistry", "publisher": "", "place": "", "date": "Jul 19, 1996", "volume": "271", "issue": "29", "section": "", "partNumber": "", "partTitle": "", "pages": "17211-17214", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Biol. Chem.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0021-9258", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 8663330", "tags": [ { "tag": "Alanine", "type": 1 }, { "tag": "Computer Graphics", "type": 1 }, { "tag": "Globins", "type": 1 }, { "tag": "Glutamic Acid", "type": 1 }, { "tag": "Hemoglobin A", "type": 1 }, { "tag": "Hemoglobin, Sickle", "type": 1 }, { "tag": "Hemoglobins", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Isoelectric Focusing", "type": 1 }, { "tag": "Kinetics", "type": 1 }, { "tag": "Macromolecular Substances", "type": 1 }, { "tag": "Models, Molecular", "type": 1 }, { "tag": "Mutagenesis, Site-Directed", "type": 1 }, { "tag": "Oxyhemoglobins", "type": 1 }, { "tag": "Point Mutation", "type": 1 }, { "tag": "Protein Conformation", "type": 1 }, { "tag": "Valine", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2013-04-15T19:50:41Z", "dateModified": "2013-04-15T19:50:41Z" } }, { "key": "HXWS6NVZ", "version": 9, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/HXWS6NVZ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/HXWS6NVZ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Reddy et al.", "parsedDate": "1997-12-16", "numChildren": 1 }, "data": { "key": "HXWS6NVZ", "version": 9, "itemType": "journalArticle", "title": "Role of beta87 Thr in the beta6 Val acceptor site during deoxy Hb S polymerization", "creators": [ { "creatorType": "author", "firstName": "L R", "lastName": "Reddy" }, { "creatorType": "author", "firstName": "K S", "lastName": "Reddy" }, { "creatorType": "author", "firstName": "S", "lastName": "Surrey" }, { "creatorType": "author", "firstName": "K", "lastName": "Adachi" } ], "abstractNote": "Three new Hb S variants containing beta87 Leu, Trp, or Asp instead of Thr were expressed in yeast in order to further define the role of the beta87 position in stability and polymerization of deoxy Hb S. Previous studies showed that hydrophobicity at beta85 Phe and beta88 Leu is critical for stabilization of hemoglobin. Results with the three Hb S beta87 variants, however, showed minimal differences in stability, suggesting that beta87 amino acid hydrophobicity is not critical for stabilization of hemoglobin. Polymerization properties of the variants in the deoxy form, however, were affected by the beta87 amino acid. Polymerization of Hb S beta87 Thr --> Leu and Hb S beta87 Thr --> Trp was preceded by a delay time like Hb S, while Hb S beta87 Thr --> Asp did not show a delay time. In addition, changes in time required for half polymer formation (T1/2) as a function of hemoglobin concentration for Hb S beta87 Thr --> Asp were similar to that for beta87 Thr --> Gln. Hb S beta87 Thr --> Leu polymerized at a lower hemoglobin concentration than Hb S while beta87 Thr --> Trp and Hb S beta87 Thr --> Asp required much higher hemoglobin concentrations for polymer formation. Critical concentration required for deoxy Hb S beta87 Thr --> Asp polymerization was 6- and 2.3-fold greater than that for Hb S beta85 Phe --> Glu and Hb S beta88 Leu --> Glu, respectively. These results suggest that even though beta87 Thr is not a direct interaction site for beta6 Val in deoxy Hb S polymers, it does play a critical role in formation of the hydrophobic acceptor pocket which then promotes protein-protein interactions facilitating formation of stable nuclei and polymers of deoxy Hb S.", "publicationTitle": "Biochemistry", "publisher": "", "place": "", "date": "Dec 16, 1997", "volume": "36", "issue": "50", "section": "", "partNumber": "", "partTitle": "", "pages": "15992-15998", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biochemistry", "DOI": "10.1021/bi9717439", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0006-2960", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 9398334", "tags": [ { "tag": "Biopolymers", "type": 1 }, { "tag": "Electrophoresis, Cellulose Acetate", "type": 1 }, { "tag": "Genetic Variation", "type": 1 }, { "tag": "Hemoglobin, Sickle", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Kinetics", "type": 1 }, { "tag": "Mutation", "type": 1 }, { "tag": "Protein Conformation", "type": 1 }, { "tag": "Protein Denaturation", "type": 1 }, { "tag": "Recombinant Proteins", "type": 1 }, { "tag": "Spectrophotometry", "type": 1 }, { "tag": "Temperature", "type": 1 }, { "tag": "Yeasts", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2013-04-15T19:25:16Z", "dateModified": "2013-04-15T19:25:16Z" } }, { "key": "4PATWZGS", "version": 9, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/4PATWZGS", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/4PATWZGS", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/HXWS6NVZ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "4PATWZGS", "version": 9, "parentItem": "HXWS6NVZ", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-04-15T19:25:16Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/9398334", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-15T19:25:16Z", "dateModified": "2013-04-15T19:25:16Z" } }, { "key": "KJGIEW7V", "version": 8, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/KJGIEW7V", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/KJGIEW7V", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/NVU6B63H", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "KJGIEW7V", "version": 8, "parentItem": "NVU6B63H", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-04-15T19:17:39Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/8021253", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-15T19:17:39Z", "dateModified": "2013-04-15T19:17:39Z" } }, { "key": "NVU6B63H", "version": 8, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/NVU6B63H", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/NVU6B63H", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Adachi et al.", "parsedDate": "1994-07-01", "numChildren": 1 }, "data": { "key": "NVU6B63H", "version": 8, "itemType": "journalArticle", "title": "Role of Leu-beta 88 in the hydrophobic acceptor pocket for Val-beta 6 during hemoglobin S polymerization", "creators": [ { "creatorType": "author", "firstName": "K", "lastName": "Adachi" }, { "creatorType": "author", "firstName": "P", "lastName": "Konitzer" }, { "creatorType": "author", "firstName": "C G", "lastName": "Paulraj" }, { "creatorType": "author", "firstName": "S", "lastName": "Surrey" } ], "abstractNote": "X-ray crystallographic studies indicate that the hydrophobic acceptor pocket made by E and F helices involving Leu-beta 88 and Phe-beta 85 is critical for the formation of stable hydrophobic interactions with Val-beta 6 on an adjacent deoxy-hemoglobin (Hb) S tetramer. Ala and Phe substitutions at the beta 88 position in Hb S were made using a yeast expression system in an effort to clarify the role of Leu-beta 88 in creating a suitable acceptor site for Val-beta 6 during polymerization of Hb S. Both Ala- and Phe-beta 88 substitutions in Hb S inhibited polymerization compared with Hb S. Critical concentrations for polymerization of alpha 2 beta 2 Val-6,Ala-88 and alpha 2 beta 2Val-6,Phe-88 were 6- and 10-fold higher, respectively, than that of Hb S (alpha 2 beta 2Val-6,Leu-88). Deoxy-Hb S containing Phe-beta 88 polymerized without a delay time like Trp-beta 6- and Phe-beta 6-substituted hemoglobins (Adachi, K., Konitzer, P., Kim, J., Welch, N., and Surrey, S. (1993) J. Biol. Chem. 268, 21650-21656). In contrast, oversaturated deoxy-Hb S containing Ala-beta 88 also polymerized without a delay time; however, with decreasing hemoglobin concentrations, the kinetics of polymerization were biphasic. At lower hemoglobin concentrations, closer to the critical concentration for polymerization, deoxy-Hb S containing Ala-beta 88 polymerized after a distinct delay time. These results suggest that bulky beta 88 hydrophobic replacements like Phe may sterically inhibit insertion of Val-beta 6 into the acceptor pocket. In contrast, smaller sized, less hydrophobic amino acids like Ala compared with Leu-beta 88 may allow insertion of Val-beta 6 into the acceptor pocket but may not promote stable protein-protein interactions with an adjacent Hb molecule. Stereospecificity and hydrophobicity of the Val-beta 6 hydrophobic acceptor pocket as well as the beta 6 amino acid are, therefore, critical for polymerization of deoxy-Hb S.", "publicationTitle": "The Journal of biological chemistry", "publisher": "", "place": "", "date": "Jul 1, 1994", "volume": "269", "issue": "26", "section": "", "partNumber": "", "partTitle": "", "pages": "17477-17480", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Biol. Chem.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0021-9258", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 8021253", "tags": [ { "tag": "Biopolymers", "type": 1 }, { "tag": "Hemoglobin, Sickle", "type": 1 }, { "tag": "Hot Temperature", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Leucine", "type": 1 }, { "tag": "Mutation", "type": 1 }, { "tag": "Oxygen", "type": 1 }, { "tag": "Recombinant Proteins", "type": 1 }, { "tag": "Valine", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2013-04-15T19:17:39Z", "dateModified": "2013-04-15T19:17:39Z" } }, { "key": "BGP68AUF", "version": 3, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/BGP68AUF", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/BGP68AUF", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/154468/items/5QNWI9TM", "type": "application/json" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } } }, "data": { "key": "BGP68AUF", "version": 3, "parentItem": "5QNWI9TM", "itemType": "attachment", "linkMode": "linked_url", "title": "Google Books Link", "accessDate": "2013-04-10T01:02:54Z", "url": "http://books.google.com/books?id=PM0zzm7wbvsC", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-04-10T01:02:54Z", "dateModified": "2013-04-10T01:02:54Z" } }, { "key": "5QNWI9TM", "version": 3, "library": { "type": "group", "id": 154468, "name": "SPARK", "links": { "alternate": { "href": "https://www.zotero.org/groups/spark", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/154468/items/5QNWI9TM", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/spark/items/5QNWI9TM", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1232890, "username": "acunningham", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/acunningham", "type": "text/html" } } }, "creatorSummary": "Steinberg", "parsedDate": "2001", "numChildren": 1 }, "data": { "key": "5QNWI9TM", "version": 3, "itemType": "book", "title": "Disorders of Hemoglobin: Genetics, Pathophysiology and Clinical Management", "creators": [ { "creatorType": "author", "firstName": "Martin H.", "lastName": "Steinberg" } ], "abstractNote": "Disorders of Hemoglobin is the first comprehensive reference on the genetic and acquired disorders of hemoglobin in over a decade. It stands as the definitive work on the genetics, pathophysiology, and clinical management of this wide range of disorders. Drs. Steinberg, Forget, Higgs, and Nagel have gathered the absolute world authorities on the science and clinical management of thalassemias, sickle cell disease, and other inherited and acquired hemoglobinopathies to create this authoritative textbook for researchers and clinicians alike. This text is divided into eight distinct sections, and includes coverage of the molecular and genetic basis of hemoglobinopathies and thalassemias, their epidemiology and genetic selection, and the diagnosis and special treatments of ^D*b and ^D*a thalassemias, sickle cell disease, Hb E, unstable hemoglobins, Hb M disorders, and acquired and secondary disorders of hemoglobin. Clinical features of all disorders are anchored to the scientific and pathophysiological events that precede them; providing clinicians with a clear scientific background of the disorders they treat, and scientists with an essential link between their research and its clinical manifestation. Disorders of Hemoglobin is the only single-source reference of its kind for hematologists, internists, pediatricians, clinical investigators, and geneticists worldwide.", "series": "", "seriesNumber": "", "volume": "", "numberOfVolumes": "", "edition": "", "date": "2001", "publisher": "Cambridge University Press", "place": "", "originalDate": "", "originalPublisher": "", "originalPlace": "", "format": "", "numPages": "1252", "ISBN": "9780521632669", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "Disorders of Hemoglobin", "language": "en", "libraryCatalog": "Google Books", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Medical / Clinical Medicine", "type": 1 }, { "tag": "Medical / Hematology", "type": 1 }, { "tag": "Medical / Oncology", "type": 1 }, { "tag": "Medical / Reference", "type": 1 }, { "tag": "Science / Life Sciences / Genetics & Genomics", "type": 1 } ], "collections": [], 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