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| - | {{Seed}} | |
| - | [[Image:3b9l.png|left|200px]] | |
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| - | <!-- | + | ==Human serum albumin complexed with myristate and AZT== |
| - | The line below this paragraph, containing "STRUCTURE_3b9l", creates the "Structure Box" on the page.
| + | <StructureSection load='3b9l' size='340' side='right'caption='[[3b9l]], [[Resolution|resolution]] 2.60Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3b9l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B9L FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZZ:3-AZIDO-3-DEOXYTHYMIDINE'>AZZ</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> |
| - | {{STRUCTURE_3b9l| PDB=3b9l | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3b9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b9l OCA], [https://pdbe.org/3b9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b9l RCSB], [https://www.ebi.ac.uk/pdbsum/3b9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b9l ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.<ref>PMID:19021548</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/3b9l_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3b9l ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA. |
| | | | |
| - | ===Human serum albumin complexed with myristate and AZT===
| + | A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography.,Zhu L, Yang F, Chen L, Meehan EJ, Huang M J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:18258455<ref>PMID:18258455</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 3b9l" style="background-color:#fffaf0;"></div> |
| | | | |
| - | <!--
| + | ==See Also== |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_18258455}}, adds the Publication Abstract to the page
| + | *[[Albumin 3D structures|Albumin 3D structures]] |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 18258455 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_18258455}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | |
| - | 3B9L is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9L OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography., Zhu L, Yang F, Chen L, Meehan EJ, Huang M, J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18258455 18258455]
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| - | | + | |
| - | Atomic structure and chemistry of human serum albumin., He XM, Carter DC, Nature. 1992 Jul 16;358(6383):209-15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1630489 1630489]
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| - | Structural basis of the drug-binding specificity of human serum albumin., Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S, J Mol Biol. 2005 Oct 14;353(1):38-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16169013 16169013]
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| - | Effect of human serum albumin on drug metabolism: structural evidence of esterase activity of human serum albumin., Yang F, Bian C, Zhu L, Zhao G, Huang Z, Huang M, J Struct Biol. 2007 Feb;157(2):348-55. Epub 2006 Sep 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17067818 17067818]
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, L.]] | + | [[Category: Chen L]] |
| - | [[Category: Huang, M.]] | + | [[Category: Huang M]] |
| - | [[Category: Meehan, E J.]] | + | [[Category: Meehan EJ]] |
| - | [[Category: Yang, F.]] | + | [[Category: Yang F]] |
| - | [[Category: Zhu, L.]] | + | [[Category: Zhu L]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Copper]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Glycation]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Lipid-binding]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein-ligands complex]]
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| - | [[Category: Secreted]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:52:47 2008''
| + | |
| Structural highlights
Disease
ALBU_HUMAN Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.[1] [2] [3] [4]
Function
ALBU_HUMAN Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.[5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA.
A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography.,Zhu L, Yang F, Chen L, Meehan EJ, Huang M J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:18258455[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S. An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7. PMID:8048949
- ↑ Rushbrook JI, Becker E, Schussler GC, Divino CM. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7. PMID:7852505
- ↑ Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50. PMID:9329347
- ↑ Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S. Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54. PMID:9589637
- ↑ Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans. 2008 Dec;36(Pt 6):1317-21. doi: 10.1042/BST0361317. PMID:19021548 doi:10.1042/BST0361317
- ↑ Zhu L, Yang F, Chen L, Meehan EJ, Huang M. A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography. J Struct Biol. 2008 Apr;162(1):40-9. Epub 2007 Dec 28. PMID:18258455 doi:10.1016/j.jsb.2007.12.004
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