5id7

From Proteopedia

(Difference between revisions)

Revision as of 07:13, 3 June 2020

Crystal structure of human serum albumin in complex with phosphorodithioate derivative of myristoyl cyclic phosphatidic acid (cPA)

Structural highlights

5id7 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, 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

Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signaling molecules, which are involved in several pathological states, such as cancer, diabetes, or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein - serum albumin.<br />Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids. Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC50 value of 29.0 muM after 24h incubation, which is almost 30% lower than IC50 of single substituted phosphorothioate cPA.<br />Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this lysophospholipid analogue. HSA binds three molecules of Myr-2S-cPA, while ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins.

Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties.,Sekula B, Ciesielska A, Rytczak P, Koziolkiewicz M, Bujacz A Biosci Rep. 2016 Apr 15. pii: BSR20160089. PMID:27129297^[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
↑ Sekula B, Ciesielska A, Rytczak P, Koziolkiewicz M, Bujacz A. Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties. Biosci Rep. 2016 Apr 15. pii: BSR20160089. PMID:27129297 doi:http://dx.doi.org/10.1042/BSR20160089

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/5id7"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human serum albumin in complex with phosphorodithioate derivative of myristoyl cyclic phosphatidic acid (cPA)==
-<StructureSection load='5id7' size='340' side='right' caption='[[5id7]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
+<StructureSection load='5id7' size='340' side='right'caption='[[5id7]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5id7]] 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=5ID7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ID7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5id7]] 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=5ID7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ID7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6A4:(4S)-2-SULFANYLIDENE-4-[(TETRADECANOYLOXY)METHYL]-1,3,2LAMBDA~5~-DIOXAPHOSPHOLANE-2-THIOLATE'>6A4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6A4:(4S)-2-SULFANYLIDENE-4-[(TETRADECANOYLOXY)METHYL]-1,3,2LAMBDA~5~-DIOXAPHOSPHOLANE-2-THIOLATE'>6A4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=5id7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id7 OCA], [http://pdbe.org/5id7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5id7 RCSB], [http://www.ebi.ac.uk/pdbsum/5id7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5id7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id7 OCA], [http://pdbe.org/5id7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5id7 RCSB], [http://www.ebi.ac.uk/pdbsum/5id7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5id7 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5id7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Albumin 3D structures|Albumin 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Bujacz, A]]
 [[Category: Bujacz, G]]

5id7

From Proteopedia

Revision as of 07:13, 3 June 2020

Crystal structure of human serum albumin in complex with phosphorodithioate derivative of myristoyl cyclic phosphatidic acid (cPA)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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