Cited 43 times in
L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin
DC Field | Value | Language |
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dc.contributor.author | 고은진 | - |
dc.date.accessioned | 2015-08-26T16:43:53Z | - |
dc.date.available | 2015-08-26T16:43:53Z | - |
dc.date.issued | 2005 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114985 | - |
dc.description.abstract | BACKGROUND: Autotaxin (ATX, NPP-2), originally purified as a potent tumor cell motility factor, is now known to be the long-sought plasma lysophospholipase D (LPLD). The integrity of the enzymatic active site, including three crucial histidine moieties, is required for motility stimulation, as well as LPLD and 5'nucleotide phosphodiesterase (PDE) activities. Except for relatively non-specific chelation agents, there are no known inhibitors of the ATX LPLD activity. RESULTS: We show that millimolar concentrations of L-histidine inhibit ATX-stimulated but not LPA-stimulated motility in two tumor cell lines, as well as inhibiting enzymatic activities. Inhibition is reversed by 20-fold lower concentrations of zinc salt. L-histidine has no significant effect on the Km of LPLD, but reduces the Vmax by greater than 50%, acting as a non-competitive inhibitor. Several histidine analogs also inhibit the LPLD activity of ATX; however, none has greater potency than L-histidine and all decrease cell viability or adhesion. CONCLUSION: L-histidine inhibition of LPLD is not a simple stoichiometric chelation of metal ions but is more likely a complex interaction with a variety of moieties, including the metal cation, at or near the active site. The inhibitory effect of L-histidine requires all three major functional groups of histidine: the alpha amino group, the alpha carboxyl group, and the metal-binding imidazole side chain. Because of LPA's involvement in pathological processes, regulation of its formation by ATX may give insight into possible novel therapeutic approaches. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1~15 | - |
dc.relation.isPartOf | LIPIDS IN HEALTH AND DISEASE | - |
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 | Cations, Divalent/chemistry | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Proliferation/drug effects | - |
dc.subject.MESH | Chelating Agents/pharmacology | - |
dc.subject.MESH | Cytokines/pharmacology* | - |
dc.subject.MESH | Enzyme Activation/drug effects | - |
dc.subject.MESH | Histidine/analogs & derivatives | - |
dc.subject.MESH | Histidine/pharmacology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lysophospholipids/biosynthesis* | - |
dc.subject.MESH | Molecular Structure | - |
dc.subject.MESH | Multienzyme Complexes/pharmacology* | - |
dc.subject.MESH | Neoplasms/metabolism* | - |
dc.subject.MESH | Neoplasms/pathology | - |
dc.subject.MESH | Phosphodiesterase I/pharmacology* | - |
dc.subject.MESH | Phosphoric Diester Hydrolases/metabolism | - |
dc.subject.MESH | Pyrophosphatases/pharmacology* | - |
dc.subject.MESH | Substrate Specificity | - |
dc.subject.MESH | Zinc/chemistry | - |
dc.subject.MESH | Zinc/pharmacology | - |
dc.title | L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry & Molecular Biology (생화학,분자생물학) | - |
dc.contributor.googleauthor | Timothy Clair | - |
dc.contributor.googleauthor | Eunjin Koh | - |
dc.contributor.googleauthor | Mary L Stracke | - |
dc.contributor.googleauthor | Elliott Schiffmann | - |
dc.contributor.googleauthor | Lance A Liotta | - |
dc.contributor.googleauthor | Russell W Bandle | - |
dc.contributor.googleauthor | Malgorzata Ptaszynska | - |
dc.identifier.doi | 10.1186/1476-511X-4-5 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00139 | - |
dc.relation.journalcode | J02169 | - |
dc.identifier.eissn | 1476-511X | - |
dc.identifier.pmid | 15737239 | - |
dc.subject.keyword | 15737239 | - |
dc.contributor.alternativeName | Koh, Eun Jin | - |
dc.contributor.affiliatedAuthor | Koh, Eun Jin | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 4 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 15 | - |
dc.identifier.bibliographicCitation | LIPIDS IN HEALTH AND DISEASE, Vol.4(5) : 1-15, 2005 | - |
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