6m5e

From Proteopedia

(Difference between revisions)

Current revision

Human serum albumin with cyclic peptide dalbavancin

Structural highlights

6m5e is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
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 peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life) is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. Small-angle X-ray scattering and isothermal titration calorimetry experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of noncovalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA.

Structural Basis for the Binding Mechanism of Human Serum Albumin Complexed with Cyclic Peptide Dalbavancin.,Ito S, Senoo A, Nagatoishi S, Ohue M, Yamamoto M, Tsumoto K, Wakui N J Med Chem. 2020 Nov 25;63(22):14045-14053. doi: 10.1021/acs.jmedchem.0c01578., Epub 2020 Nov 13. PMID:33183011^[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
↑ Ito S, Senoo A, Nagatoishi S, Ohue M, Yamamoto M, Tsumoto K, Wakui N. Structural Basis for the Binding Mechanism of Human Serum Albumin Complexed with Cyclic Peptide Dalbavancin. J Med Chem. 2020 Nov 25;63(22):14045-14053. doi: 10.1021/acs.jmedchem.0c01578., Epub 2020 Nov 13. PMID:33183011 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c01578

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/6m5e"

@@ Line 1: / Line 1: @@
-====
+==Human serum albumin with cyclic peptide dalbavancin==
-<StructureSection load='6m5e' size='340' side='right'caption='[[6m5e]]' scene=''>
+<StructureSection load='6m5e' size='340' side='right'caption='[[6m5e]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6m5e]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M5E FirstGlance]. <br>
-</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=6m5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m5e OCA], [http://pdbe.org/6m5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m5e RCSB], [http://www.ebi.ac.uk/pdbsum/6m5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m5e ProSAT]</span></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]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5PG:(2S)-(4-HYDROXYPHENYL)(METHYLAMINO)ETHANOIC+ACID'>5PG</scene>, <scene name='pdbligand=D3P:(2R)-AMINO(3,5-DIHYDROXYPHENYL)ACETIC+ACID'>D3P</scene>, <scene name='pdbligand=D4P:(2S)-AMINO(4-HYDROXYPHENYL)ACETIC+ACID'>D4P</scene>, <scene name='pdbligand=DIB:3-AMINO-(DIMETHYLPROPYLAMINE)'>DIB</scene>, <scene name='pdbligand=F8F:(2S,5S)-5-azanyl-3,4,6-tris(oxidanyl)oxane-2-carboxylic+acid'>F8F</scene>, <scene name='pdbligand=F8X:2-amino-2-deoxy-beta-D-altropyranuronic+acid'>F8X</scene>, <scene name='pdbligand=F93:(2R,3S)-2-azanyl-3-(3-chloranyl-4-oxidanyl-phenyl)-3-oxidanyl-propanoic+acid'>F93</scene>, <scene name='pdbligand=HCL:(2S)-2-AZANYL-2-[2-CHLORANYL-3,5-BIS(OXIDANYL)PHENYL]ETHANOIC+ACID'>HCL</scene>, <scene name='pdbligand=JEF:O-(O-(2-AMINOPROPYL)-O-(2-METHOXYETHYL)POLYPROPYLENE+GLYCOL+500)'>JEF</scene>, <scene name='pdbligand=M12:10-METHYLUNDECANOIC+ACID'>M12</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=OMZ:(BETAR)-3-CHLORO-BETA-HYDROXY-D-TYROSINE'>OMZ</scene>, <scene name='pdbligand=WOO:BETA-L-ALLOPYRANOSE'>WOO</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=6m5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m5e OCA], [https://pdbe.org/6m5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m5e RCSB], [https://www.ebi.ac.uk/pdbsum/6m5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m5e 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 ==
+Cyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life) is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. Small-angle X-ray scattering and isothermal titration calorimetry experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of noncovalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA.
+Structural Basis for the Binding Mechanism of Human Serum Albumin Complexed with Cyclic Peptide Dalbavancin.,Ito S, Senoo A, Nagatoishi S, Ohue M, Yamamoto M, Tsumoto K, Wakui N J Med Chem. 2020 Nov 25;63(22):14045-14053. doi: 10.1021/acs.jmedchem.0c01578., Epub 2020 Nov 13. PMID:33183011<ref>PMID:33183011</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6m5e" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Synthetic construct]]
+[[Category: Ito S]]
+[[Category: Nagatoishi S]]
+[[Category: Ohue M]]
+[[Category: Senoo A]]
+[[Category: Tsumoto K]]
+[[Category: Wakui N]]
+[[Category: Yamamoto M]]

6m5e

From Proteopedia

Current revision

Human serum albumin with cyclic peptide dalbavancin

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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