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| - | [[Image:1o9x.gif|left|200px]]<br /><applet load="1o9x" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1o9x, resolution 3.20Å" /> | |
| - | '''HUMAN SERUM ALBUMIN COMPLEXED WITH TETRADECANOIC ACID (MYRISTIC ACID) AND HEMIN'''<br /> | |
| | | | |
| - | ==Overview== | + | ==HUMAN SERUM ALBUMIN COMPLEXED WITH TETRADECANOIC ACID (MYRISTIC ACID) AND HEMIN== |
| - | BACKGROUND: Human serum albumin (HSA) is an abundant plasma protein that, binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind, oxygen reversibly, it may be possible to develop modified HSA proteins or, heme groups that will confer this ability on the complex. RESULTS: We, present here the crystal structure of a ternary HSA-hemin-myristate, complex, formed at a 1:1:4 molar ratio, that contains a single hemin group, bound to subdomain IB and myristate bound at six sites. The complex, displays a conformation that is intermediate between defatted HSA and, HSA-fatty acid complexes; this is likely to be due to low myristate, occupancy in the fatty acid binding sites that drive the conformational, change. The hemin group is bound within a narrow D-shaped hydrophobic, cavity which usually accommodates fatty acid; the hemin propionate groups, are coordinated by a triad of basic residues at the pocket entrance. The, iron atom in the centre of the hemin is coordinated by Tyr161. CONCLUSION:, The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the, key polar and hydrophobic interactions that determine the hemin-binding, specificity of HSA. The details of the hemin-binding environment of HSA, provide a structural foundation for efforts to modify the protein and/or, the heme molecule in order to engineer complexes that have favourable, oxygen-binding properties. | + | <StructureSection load='1o9x' size='340' side='right'caption='[[1o9x]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1o9x]] 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=1O9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O9X FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1o9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o9x OCA], [https://pdbe.org/1o9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o9x RCSB], [https://www.ebi.ac.uk/pdbsum/1o9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o9x 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/o9/1o9x_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=1o9x ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | BACKGROUND: Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. RESULTS: We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. CONCLUSION: The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties. |
| | | | |
| - | ==Disease==
| + | Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.,Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S BMC Struct Biol. 2003 Jul 7;3:6. Epub 2003 Jul 7. PMID:12846933<ref>PMID:12846933</ref> |
| - | Known diseases associated with this structure: Analbuminemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]], Dysalbuminemic hyperthyroxinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]], Dysalbuminemic hyperzincemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600 103600]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1O9X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MYR:'>MYR</scene> and <scene name='pdbligand=HEM:'>HEM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Hem+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O9X OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1o9x" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Crystal structural analysis of human serum albumin complexed with hemin and fatty acid., Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S, BMC Struct Biol. 2003 Jul 7;3:6. Epub 2003 Jul 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12846933 12846933]
| + | *[[Albumin 3D structures|Albumin 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Curry, S.]] | + | [[Category: Curry S]] |
| - | [[Category: Ghuman, J.]] | + | [[Category: Ghuman J]] |
| - | [[Category: Komatsu, T.]] | + | [[Category: Komatsu T]] |
| - | [[Category: Tsuchida, E.]] | + | [[Category: Tsuchida E]] |
| - | [[Category: Zunszain, P.A.]] | + | [[Category: Zunszain PA]] |
| - | [[Category: HEM]]
| + | |
| - | [[Category: MYR]]
| + | |
| - | [[Category: fatty acid transport]]
| + | |
| - | [[Category: heme-binding]]
| + | |
| - | [[Category: lipid-binding]]
| + | |
| - | [[Category: plasma protein]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:55:24 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
BACKGROUND: Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. RESULTS: We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. CONCLUSION: The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties.
Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.,Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S BMC Struct Biol. 2003 Jul 7;3:6. Epub 2003 Jul 7. PMID:12846933[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
- ↑ Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S. Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol. 2003 Jul 7;3:6. Epub 2003 Jul 7. PMID:12846933 doi:10.1186/1472-6807-3-6
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