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2ydf

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Revision as of 09:49, 4 August 2016

HUMAN SERUM ALBUMIN COMPLEXED WITH IOPHENOXIC ACID

Structural highlights

2ydf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2bxq, 1hk4, 2xvu, 2bxi, 2vuf, 2xvv, 1o9x, 1bke, 2bxk, 1hk1, 1uor, 1h9z, 1e7b, 1hk2, 1hk5, 2esg, 1e7e, 2xvq, 2bxg, 2bxh, 2bxo, 2bxf, 1ysx, 1e7g, 1ao6, 2bxc, 2bxe, 1tf0, 2bxn, 1e7c, 1gnj, 2xw0, 1e7h, 2bxa, 1hk3, 2xsi, 2xvw, 2bxb, 2xw1, 1e7i, 2bxl, 1gni, 1ha2, 1bj5, 1e7a, 2bxp, 2bxd, 1bm0, 1e78, 2vdb, 1e7f, 1n5u, 2bxm, 2bx8, 2vue
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

ABSTRACT: BACKGROUND: Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. RESULTS: We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 A resolution, revealing a total of four binding sites, two of which -- in drugs sites 1 and 2 on the protein -- are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. CONCLUSIONS: The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.

Crystallographic analysis reveals the structural basis of the high-affinity binding of Iophenoxic acid to Human Serum Albumin.,Ryan AJ, Chung CW, Curry S BMC Struct Biol. 2011 Apr 18;11(1):18. PMID:21501503^[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
↑ Ryan AJ, Chung CW, Curry S. Crystallographic analysis reveals the structural basis of the high-affinity binding of Iophenoxic acid to Human Serum Albumin. BMC Struct Biol. 2011 Apr 18;11(1):18. PMID:21501503 doi:10.1186/1472-6807-11-18

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ydf"

Categories: Human | Curry, S | Ryan, A J | Transport protein

@@ Line 1: / Line 1: @@
 ==HUMAN SERUM ALBUMIN COMPLEXED WITH IOPHENOXIC ACID==
 <StructureSection load='2ydf' size='340' side='right' caption='[[2ydf]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ydf]] is a 2 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=2YDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YDF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ydf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YDF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IO3:IOPHENOXIC+ACID'>IO3</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bxq|2bxq]], [[1hk4|1hk4]], [[2xvu|2xvu]], [[2bxi|2bxi]], [[2vuf|2vuf]], [[2xvv|2xvv]], [[1o9x|1o9x]], [[1bke|1bke]], [[2bxk|2bxk]], [[1hk1|1hk1]], [[1uor|1uor]], [[1h9z|1h9z]], [[1e7b|1e7b]], [[1hk2|1hk2]], [[1hk5|1hk5]], [[2esg|2esg]], [[1e7e|1e7e]], [[2xvq|2xvq]], [[2bxg|2bxg]], [[2bxh|2bxh]], [[2bxo|2bxo]], [[2bxf|2bxf]], [[1ysx|1ysx]], [[1e7g|1e7g]], [[1ao6|1ao6]], [[2bxc|2bxc]], [[2bxe|2bxe]], [[1tf0|1tf0]], [[2bxn|2bxn]], [[1e7c|1e7c]], [[1gnj|1gnj]], [[2xw0|2xw0]], [[1e7h|1e7h]], [[2bxa|2bxa]], [[1hk3|1hk3]], [[2xsi|2xsi]], [[2xvw|2xvw]], [[2bxb|2bxb]], [[2xw1|2xw1]], [[1e7i|1e7i]], [[2bxl|2bxl]], [[1gni|1gni]], [[1ha2|1ha2]], [[1bj5|1bj5]], [[1e7a|1e7a]], [[2bxp|2bxp]], [[2bxd|2bxd]], [[1bm0|1bm0]], [[1e78|1e78]], [[2vdb|2vdb]], [[1e7f|1e7f]], [[1n5u|1n5u]], [[2bxm|2bxm]], [[2bx8|2bx8]], [[2vue|2vue]]</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=2ydf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ydf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ydf RCSB], [http://www.ebi.ac.uk/pdbsum/2ydf 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=2ydf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ydf OCA], [http://pdbe.org/2ydf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ydf RCSB], [http://www.ebi.ac.uk/pdbsum/2ydf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ydf ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2ydf" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Curry, S]]
 [[Category: Ryan, A J]]
 [[Category: Transport protein]]

2ydf

From Proteopedia

Revision as of 09:49, 4 August 2016

HUMAN SERUM ALBUMIN COMPLEXED WITH IOPHENOXIC ACID

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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