6ezq

From Proteopedia

(Difference between revisions)

Current revision

human Serum Albumin complexed with NBD-C12 fatty acid

Structural highlights

6ezq 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.
Method:	X-ray diffraction, Resolution 2.39Å
Ligands:
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

A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using a NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein, which are important prerequisites for modulation of drug pharmacokinetics.

Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin.,Petry S, Wenskowsky L, Schreuder H, Derdau V, Matter H, Volkmar J, Opatz T Angew Chem Int Ed Engl. 2017 Nov 28. doi: 10.1002/anie.201710437. PMID:29193545^[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
↑ Petry S, Wenskowsky L, Schreuder H, Derdau V, Matter H, Volkmar J, Opatz T. Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin. Angew Chem Int Ed Engl. 2017 Nov 28. doi: 10.1002/anie.201710437. PMID:29193545 doi:http://dx.doi.org/10.1002/anie.201710437

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/6ezq"

Categories: Homo sapiens | Large Structures | Liesum A | Schreuder HA | Wenskowsky L

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6ezq is ON HOLD
+==human Serum Albumin complexed with NBD-C12 fatty acid==
+<StructureSection load='6ezq' size='340' side='right'caption='[[6ezq]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ezq]] 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=6EZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EZQ 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]] 2.39&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C7K:12-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]dodecanoic+acid'>C7K</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=6ezq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ezq OCA], [https://pdbe.org/6ezq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ezq RCSB], [https://www.ebi.ac.uk/pdbsum/6ezq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ezq 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 ==
+A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using a NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein, which are important prerequisites for modulation of drug pharmacokinetics.
-Authors: Wenskowsky, L., Liesum, A., Schreuder, H.A.
+Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin.,Petry S, Wenskowsky L, Schreuder H, Derdau V, Matter H, Volkmar J, Opatz T Angew Chem Int Ed Engl. 2017 Nov 28. doi: 10.1002/anie.201710437. PMID:29193545<ref>PMID:29193545</ref>
-Description: human Serum Albumin complexed with NBD-C12 fatty acid
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Liesum, A]]
+<div class="pdbe-citations 6ezq" style="background-color:#fffaf0;"></div>
-[[Category: Wenskowsky, L]]
-[[Category: Schreuder, H.A]]
+==See Also==
+*[[Albumin 3D structures|Albumin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Liesum A]]
+[[Category: Schreuder HA]]
+[[Category: Wenskowsky L]]

6ezq

From Proteopedia

Current revision

human Serum Albumin complexed with NBD-C12 fatty 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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