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L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin

DC FieldValueLanguage
dc.contributor.author고은진-
dc.date.accessioned2015-08-26T16:43:53Z-
dc.date.available2015-08-26T16:43:53Z-
dc.date.issued2005-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/114985-
dc.description.abstractBACKGROUND: 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.statementOfResponsibilityopen-
dc.format.extent1~15-
dc.relation.isPartOfLIPIDS IN HEALTH AND DISEASE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHCations, Divalent/chemistry-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Proliferation/drug effects-
dc.subject.MESHChelating Agents/pharmacology-
dc.subject.MESHCytokines/pharmacology*-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHHistidine/analogs & derivatives-
dc.subject.MESHHistidine/pharmacology*-
dc.subject.MESHHumans-
dc.subject.MESHLysophospholipids/biosynthesis*-
dc.subject.MESHMolecular Structure-
dc.subject.MESHMultienzyme Complexes/pharmacology*-
dc.subject.MESHNeoplasms/metabolism*-
dc.subject.MESHNeoplasms/pathology-
dc.subject.MESHPhosphodiesterase I/pharmacology*-
dc.subject.MESHPhosphoric Diester Hydrolases/metabolism-
dc.subject.MESHPyrophosphatases/pharmacology*-
dc.subject.MESHSubstrate Specificity-
dc.subject.MESHZinc/chemistry-
dc.subject.MESHZinc/pharmacology-
dc.titleL-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biochemistry & Molecular Biology (생화학,분자생물학)-
dc.contributor.googleauthorTimothy Clair-
dc.contributor.googleauthorEunjin Koh-
dc.contributor.googleauthorMary L Stracke-
dc.contributor.googleauthorElliott Schiffmann-
dc.contributor.googleauthorLance A Liotta-
dc.contributor.googleauthorRussell W Bandle-
dc.contributor.googleauthorMalgorzata Ptaszynska-
dc.identifier.doi10.1186/1476-511X-4-5-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00139-
dc.relation.journalcodeJ02169-
dc.identifier.eissn1476-511X-
dc.identifier.pmid15737239-
dc.subject.keyword15737239-
dc.contributor.alternativeNameKoh, Eun Jin-
dc.contributor.affiliatedAuthorKoh, Eun Jin-
dc.rights.accessRightsfree-
dc.citation.volume4-
dc.citation.number5-
dc.citation.startPage1-
dc.citation.endPage15-
dc.identifier.bibliographicCitationLIPIDS IN HEALTH AND DISEASE, Vol.4(5) : 1-15, 2005-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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