7aai

From Proteopedia

(Difference between revisions)

Revision as of 10:46, 31 March 2021

Crystal structure of Human serum albumin in complex with perfluorooctanoic acid (PFOA) at 2.10 Angstrom Resolution

Structural highlights

7aai is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Gene:	ALB, GIG20, GIG42, PRO0903, PRO1708, PRO2044, PRO2619, PRO2675, UNQ696/PRO1341 (HUMAN)
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

Perfluorooctanoic acid (PFOA) is a toxic compound that is absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human serum albumin (hSA). Though the interaction between PFOA and hSA has been already assessed using various analytical techniques, a high resolution and detailed analysis of the binding mode is still lacking. We report here the crystal structure of hSA in complex with PFOA and a medium-chain saturated fatty acid (FA). A total of eight distinct binding sites, four occupied by PFOAs and four by FAs, have been identified. In solution binding studies confirmed the 4:1 PFOA-hSA stoichiometry and revealed the presence of one high and three low affinity binding sites. Competition experiments with known hSA-binding drugs allowed locating the high affinity binding site in sub-domain IIIA. The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications. This article is protected by copyright. All rights reserved.

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin.,Maso L, Trande M, Liberi S, Moro G, Daems E, Linciano S, Sobott F, Covaceuszach S, Cassetta A, Fasolato S, Moretto LM, De Wael K, Cendron L, Angelini A Protein Sci. 2021 Feb 7. doi: 10.1002/pro.4036. PMID:33550662^[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
↑ Maso L, Trande M, Liberi S, Moro G, Daems E, Linciano S, Sobott F, Covaceuszach S, Cassetta A, Fasolato S, Moretto LM, De Wael K, Cendron L, Angelini A. Unveiling the binding mode of perfluorooctanoic acid to human serum albumin. Protein Sci. 2021 Feb 7. doi: 10.1002/pro.4036. PMID:33550662 doi:http://dx.doi.org/10.1002/pro.4036

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/7aai"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Human serum albumin in complex with perfluorooctanoic acid (PFOA) at 2.10 Angstrom Resolution==
-<StructureSection load='7aai' size='340' side='right'caption='[[7aai]]' scene=''>
+<StructureSection load='7aai' size='340' side='right'caption='[[7aai]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AAI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7aai]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AAI FirstGlance]. <br>
-</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=7aai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aai OCA], [https://pdbe.org/7aai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aai RCSB], [https://www.ebi.ac.uk/pdbsum/7aai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aai ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8PF:PENTADECAFLUOROOCTANOIC+ACID'>8PF</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALB, GIG20, GIG42, PRO0903, PRO1708, PRO2044, PRO2619, PRO2675, UNQ696/PRO1341 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7aai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aai OCA], [https://pdbe.org/7aai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aai RCSB], [https://www.ebi.ac.uk/pdbsum/7aai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aai 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Perfluorooctanoic acid (PFOA) is a toxic compound that is absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human serum albumin (hSA). Though the interaction between PFOA and hSA has been already assessed using various analytical techniques, a high resolution and detailed analysis of the binding mode is still lacking. We report here the crystal structure of hSA in complex with PFOA and a medium-chain saturated fatty acid (FA). A total of eight distinct binding sites, four occupied by PFOAs and four by FAs, have been identified. In solution binding studies confirmed the 4:1 PFOA-hSA stoichiometry and revealed the presence of one high and three low affinity binding sites. Competition experiments with known hSA-binding drugs allowed locating the high affinity binding site in sub-domain IIIA. The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications. This article is protected by copyright. All rights reserved.
+Unveiling the binding mode of perfluorooctanoic acid to human serum albumin.,Maso L, Trande M, Liberi S, Moro G, Daems E, Linciano S, Sobott F, Covaceuszach S, Cassetta A, Fasolato S, Moretto LM, De Wael K, Cendron L, Angelini A Protein Sci. 2021 Feb 7. doi: 10.1002/pro.4036. PMID:33550662<ref>PMID:33550662</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7aai" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Albumin 3D structures|Albumin 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Angelini A]]
+[[Category: Angelini, A]]
-[[Category: Cendron L]]
+[[Category: Cendron, L]]
-[[Category: Liberi S]]
+[[Category: Liberi, S]]
-[[Category: Maso L]]
+[[Category: Maso, L]]
-[[Category: Trande M]]
+[[Category: Trande, M]]
+[[Category: Drug carrier]]
+[[Category: Lipid binding protein]]
+[[Category: Protein transport]]
+[[Category: Serum protein]]

7aai

From Proteopedia

Revision as of 10:46, 31 March 2021

Crystal structure of Human serum albumin in complex with perfluorooctanoic acid (PFOA) at 2.10 Angstrom Resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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