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| | ==human Serum Albumin complexed with NBD-C12 fatty acid== | | ==human Serum Albumin complexed with NBD-C12 fatty acid== |
| - | <StructureSection load='6ezq' size='340' side='right' caption='[[6ezq]], [[Resolution|resolution]] 2.39Å' scene=''> | + | <StructureSection load='6ezq' size='340' side='right'caption='[[6ezq]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ezq]] 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=6EZQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EZQ FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C7K:12-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]dodecanoic+acid'>C7K</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.39Å</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=6ezq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ezq OCA], [http://pdbe.org/6ezq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ezq RCSB], [http://www.ebi.ac.uk/pdbsum/6ezq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ezq ProSAT]</span></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> | | </table> |
| | == Disease == | | == 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> | + | [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 == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ezq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ezq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Albumin 3D structures|Albumin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Liesum, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Schreuder, H A]] | + | [[Category: Liesum A]] |
| - | [[Category: Wenskowsky, L]] | + | [[Category: Schreuder HA]] |
| - | [[Category: Fatty acid binding site human serum albumin nbd label drug interaction]] | + | [[Category: Wenskowsky L]] |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
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.
See Also
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
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