This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1h9z

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 23:38, 22 December 2014

HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID AND THE R-(+) ENANTIOMER OF WARFARIN

Structural highlights

1h9z is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1ao6, 1bj5, 1bke, 1bm0, 1e78, 1e7a, 1e7b, 1e7c, 1e7e, 1e7f, 1e7g, 1e7h, 1e7i, 1uor, 1ha2
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid.

Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I.,Petitpas I, Bhattacharya AA, Twine S, East M, Curry S J Biol Chem. 2001 Jun 22;276(25):22804-9. Epub 2001 Apr 2. PMID:11285262^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Petitpas I, Bhattacharya AA, Twine S, East M, Curry S. Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J Biol Chem. 2001 Jun 22;276(25):22804-9. Epub 2001 Apr 2. PMID:11285262 doi:http://dx.doi.org/10.1074/jbc.M100575200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1h9z"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1h9z]] is a 1 chain structure with 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=1H9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H9Z FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=RWF:R-WARFARIN'>RWF</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=RWF:R-WARFARIN'>RWF</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ao6|1ao6]], [[1bj5|1bj5]], [[1bke|1bke]], [[1bm0|1bm0]], [[1e78|1e78]], [[1e7a|1e7a]], [[1e7b|1e7b]], [[1e7c|1e7c]], [[1e7e|1e7e]], [[1e7f|1e7f]], [[1e7g|1e7g]], [[1e7h|1e7h]], [[1e7i|1e7i]], [[1uor|1uor]], [[1ha2|1ha2]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ao6|1ao6]], [[1bj5|1bj5]], [[1bke|1bke]], [[1bm0|1bm0]], [[1e78|1e78]], [[1e7a|1e7a]], [[1e7b|1e7b]], [[1e7c|1e7c]], [[1e7e|1e7e]], [[1e7f|1e7f]], [[1e7g|1e7g]], [[1e7h|1e7h]], [[1e7i|1e7i]], [[1uor|1uor]], [[1ha2|1ha2]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h9z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h9z RCSB], [http://www.ebi.ac.uk/pdbsum/1h9z PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h9z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h9z RCSB], [http://www.ebi.ac.uk/pdbsum/1h9z PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN]] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[http://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>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bhattacharya, A A.]]
+[[Category: Bhattacharya, A A]]
-[[Category: Curry, S.]]
+[[Category: Curry, S]]
-[[Category: Petitpas, I.]]
+[[Category: Petitpas, I]]
 [[Category: Anti-coagulant]]
 [[Category: Drug binding]]
 [[Category: Serum protein]]
 [[Category: Transport protein]]

1h9z

From Proteopedia

Revision as of 23:38, 22 December 2014

HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID AND THE R-(+) ENANTIOMER OF WARFARIN

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox