8itt

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of lysophosphatidylcholine in complex with human serum albumin and myristate

Structural highlights

8itt 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.
Method:	X-ray diffraction, Resolution 3.03Å
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

Lysophospholipids (lysoPLs) are crucial metabolites involved in various physiological and pathological cellular processes. Understanding their binding interactions, particularly with human serum albumin (HSA), is essential due to their role in regulating lysoPLs-induced cytotoxicity. However, the precise mechanism of lysoPLs binding to HSA remains elusive. In this study, we employed fluorescence quenching and optical interferometry assays to demonstrate direct binding between lysophosphatidylcholine (LPC) and HSA (K(D) = 25 muM). Furthermore, we determined crystal structures of HSA in complex with LPC, both in the absence and the presence of the endogenous fatty acid myristate (14:0). The crystal structure of binary HSA:LPC revealed that six LPC molecules are bound to HSA at the primary fatty acid binding sites. Interestingly, the ternary HSA:Myr:LPC structure demonstrated the continued binding of three LPC molecules to HSA at binding sites 1, 3, and 5 in the presence of myristate. These findings support HSA's role as a carrier protein for lysoPLs in blood plasma and provide valuable insights into the structural basis of their binding mechanisms.

Crystal structures of human serum albumin in complex with lysophosphatidylcholine.,Wang Y, Luo Z, Morelli X, Xu P, Jiang L, Shi X, Huang M Biophys J. 2023 Nov 7;122(21):4135-4143. doi: 10.1016/j.bpj.2023.09.007. Epub , 2023 Sep 19. PMID:37731243^[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
↑ Wang Y, Luo Z, Morelli X, Xu P, Jiang L, Shi X, Huang M. Crystal structures of human serum albumin in complex with lysophosphatidylcholine. Biophys J. 2023 Nov 7;122(21):4135-4143. PMID:37731243 doi:10.1016/j.bpj.2023.09.007

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8itt"

Categories: Homo sapiens | Large Structures | Huang MD | Jiang LG | Wang Y

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8itt is ON HOLD
+==Crystal structure of lysophosphatidylcholine in complex with human serum albumin and myristate==
+<StructureSection load='8itt' size='340' side='right'caption='[[8itt]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8itt]] is a 2 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=8ITT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ITT 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]] 3.03&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LPC:[1-MYRISTOYL-GLYCEROL-3-YL]PHOSPHONYLCHOLINE'>LPC</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=8itt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8itt OCA], [https://pdbe.org/8itt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8itt RCSB], [https://www.ebi.ac.uk/pdbsum/8itt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8itt 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 ==
+Lysophospholipids (lysoPLs) are crucial metabolites involved in various physiological and pathological cellular processes. Understanding their binding interactions, particularly with human serum albumin (HSA), is essential due to their role in regulating lysoPLs-induced cytotoxicity. However, the precise mechanism of lysoPLs binding to HSA remains elusive. In this study, we employed fluorescence quenching and optical interferometry assays to demonstrate direct binding between lysophosphatidylcholine (LPC) and HSA (K(D) = 25 muM). Furthermore, we determined crystal structures of HSA in complex with LPC, both in the absence and the presence of the endogenous fatty acid myristate (14:0). The crystal structure of binary HSA:LPC revealed that six LPC molecules are bound to HSA at the primary fatty acid binding sites. Interestingly, the ternary HSA:Myr:LPC structure demonstrated the continued binding of three LPC molecules to HSA at binding sites 1, 3, and 5 in the presence of myristate. These findings support HSA's role as a carrier protein for lysoPLs in blood plasma and provide valuable insights into the structural basis of their binding mechanisms.
-Authors: Wang, Y., Jiang, L.G., Huang, M.D.
+Crystal structures of human serum albumin in complex with lysophosphatidylcholine.,Wang Y, Luo Z, Morelli X, Xu P, Jiang L, Shi X, Huang M Biophys J. 2023 Nov 7;122(21):4135-4143. doi: 10.1016/j.bpj.2023.09.007. Epub , 2023 Sep 19. PMID:37731243<ref>PMID:37731243</ref>
-Description: Crystal structure of lysophosphatidylcholine in complex with human serum albumin and myristate
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Huang, M.D]]
+<div class="pdbe-citations 8itt" style="background-color:#fffaf0;"></div>
-[[Category: Wang, Y]]
+== References ==
-[[Category: Jiang, L.G]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Huang MD]]
+[[Category: Jiang LG]]
+[[Category: Wang Y]]

8itt

From Proteopedia

Current revision

Crystal structure of lysophosphatidylcholine in complex with human serum albumin and myristate

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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