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3a73

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Revision as of 08:18, 20 January 2015

Crystal Structure Analysis of Human serum albumin complexed with delta 12-prostaglandin J2

Structural highlights

3a73 is a 2 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:	,
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), the most abundant protein in plasma, has a very unique function, catalyzing the conversion of prostaglandin J(2) (PGJ(2)), a dehydration product of PGD(2), to yield Delta(12)-PGJ(2). These PGD(2) metabolites are actively transported into cells and accumulated in the nuclei, where they act as potent inducers of cell growth inhibition and cell differentiation, and exhibit their own unique spectrum of biological effects. The facts that (i) arachidonic acid metabolites bind to human serum albumin (HSA) and the metabolism of these molecules is altered as a result of binding, (ii) HSA catalyzes the transformation of PGJ(2) into Delta(12)-PGJ(2), and (iii) Delta(12)-PGJ(2) is stable in serum suggest that HSA may bind and stabilize Delta(12)-PGJ(2) in a specific manner. A molecular interaction analysis using surface plasmon resonance (Biacore) indeed suggested the presence of a specific Delta(12)-PGJ(2)-binding site in HSA. To investigate the molecular details of the binding of this PGD(2) metabolite to albumin, we analyzed the cocrystal structure of the HSA-Delta(12)-PGJ(2)-myristate complex by X-ray crystallography and found that two Delta(12)-PGJ(2) molecules bind to a primary site in subdomain IB of the protein. The electron density results suggested that one of the two Delta(12)-PGJ(2) molecules that specifically bind to the site covalently interacted with a histidine residue (His146). Using nano-LC-MS/MS analysis of the HSA-Delta(12)-PGJ(2) complex, the formation of an unusual Delta(12)-PGJ(2)-histidine adduct at His146 was confirmed. Thus, our crystallographic and mass spectrometric analyses of the HSA-Delta(12)-PGJ(2) complex provided intriguing new insights into the molecular details of how this electrophilic ligand interacts with its primary producer and transporter.

Delta12-prostaglandin J2 as a product and ligand of human serum albumin: formation of an unusual covalent adduct at His146.,Yamaguchi S, Aldini G, Ito S, Morishita N, Shibata T, Vistoli G, Carini M, Uchida K J Am Chem Soc. 2010 Jan 20;132(2):824-32. PMID:20014793^[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
↑ Yamaguchi S, Aldini G, Ito S, Morishita N, Shibata T, Vistoli G, Carini M, Uchida K. Delta12-prostaglandin J2 as a product and ligand of human serum albumin: formation of an unusual covalent adduct at His146. J Am Chem Soc. 2010 Jan 20;132(2):824-32. PMID:20014793 doi:10.1021/ja908878n

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/3a73"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3a73]] 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=3A73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3A73 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=PJ2:(5Z,12Z,15S)-15-HYDROXY-11-OXOPROSTA-5,9,12-TRIEN-1-OIC+ACID'>PJ2</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=PJ2:(5Z,12Z,15S)-15-HYDROXY-11-OXOPROSTA-5,9,12-TRIEN-1-OIC+ACID'>PJ2</scene></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=3a73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3a73 RCSB], [http://www.ebi.ac.uk/pdbsum/3a73 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=3a73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3a73 RCSB], [http://www.ebi.ac.uk/pdbsum/3a73 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 36: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ito, S.]]
+[[Category: Ito, S]]
 [[Category: Alpha-helical strcture]]
 [[Category: Cleavage on pair of basic residue]]

3a73

From Proteopedia

Revision as of 08:18, 20 January 2015

Crystal Structure Analysis of Human serum albumin complexed with delta 12-prostaglandin J2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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