Cited 29 times in
Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김종선 | - |
dc.contributor.author | 박전한 | - |
dc.date.accessioned | 2016-05-16T11:25:25Z | - |
dc.date.available | 2016-05-16T11:25:25Z | - |
dc.date.issued | 2002 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/144517 | - |
dc.description.abstract | Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Together with protein tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular signaling processes. In this study, diverse compounds were screened for PTP inhibition and selectively screened for inhibitors with the end product inhibition properties. Among phosphate analogues and their derivatives for PTP inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT) strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 µM in the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM and PT were not significantly affected by EDTA. PM and PT were potent, competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution, reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The molybdenium atom of the inhibitor is coordinated with six ligands: three oxo-ligands, two apical water molecules and a S atom of the catalytic cysteine residue. In support of the crystallographic finding, we observed that molybdenium oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the range 5-15 µM. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 211~223 | - |
dc.relation.isPartOf | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Binding, Competitive | - |
dc.subject.MESH | Catalytic Domain | - |
dc.subject.MESH | Crystallography, X-Ray | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Drug Evaluation, Preclinical | - |
dc.subject.MESH | Edetic Acid/pharmacology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Inhibitory Concentration 50 | - |
dc.subject.MESH | Kinetics | - |
dc.subject.MESH | Models, Molecular | - |
dc.subject.MESH | Molybdenum/pharmacology* | - |
dc.subject.MESH | Phosphoric Acids/pharmacology* | - |
dc.subject.MESH | Protein Structure, Tertiary | - |
dc.subject.MESH | Protein Tyrosine Phosphatases/antagonists & inhibitors* | - |
dc.subject.MESH | Protein Tyrosine Phosphatases/chemistry* | - |
dc.subject.MESH | Protein Tyrosine Phosphatases/isolation & purification | - |
dc.subject.MESH | Substrate Specificity | - |
dc.subject.MESH | Tungsten Compounds/pharmacology* | - |
dc.title | Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Microbiology (미생물학) | - |
dc.contributor.googleauthor | Yong-Seok Heo | - |
dc.contributor.googleauthor | Jung Min Ryu | - |
dc.contributor.googleauthor | Sang Myun Park | - |
dc.contributor.googleauthor | Jeon Han Park | - |
dc.contributor.googleauthor | Hyun-Chul Lee | - |
dc.contributor.googleauthor | Kwang Yeon Hwang | - |
dc.contributor.googleauthor | Jong Sun Kim | - |
dc.identifier.doi | 10.1038/emm.2002.30 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00921 | - |
dc.contributor.localId | A01641 | - |
dc.relation.journalcode | J00860 | - |
dc.identifier.eissn | 2092-6413 | - |
dc.identifier.pmid | 12216113 | - |
dc.contributor.alternativeName | Kim, Jong Sun | - |
dc.contributor.alternativeName | Park, Jeon Han | - |
dc.contributor.affiliatedAuthor | Kim, Jong Sun | - |
dc.contributor.affiliatedAuthor | Park, Jeon Han | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 34 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 211 | - |
dc.citation.endPage | 223 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.34(3) : 211-223, 2002 | - |
dc.identifier.rimsid | 49772 | - |
dc.type.rims | ART | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.