دورية أكاديمية
L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin
| العنوان: | L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin |
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| المساهمون: | Timothy Clair, Eunjin Koh, Mary L Stracke, Elliott Schiffmann, Lance A Liotta, Russell W Bandle, Malgorzata Ptaszynska, Koh, Eun Jin |
| المصدر: | T200505082.pdf |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Cations, Divalent/chemistry, Cell Line, Tumor, Cell Proliferation/drug effects, Chelating Agents/pharmacology, Cytokines/pharmacology, Enzyme Activation/drug effects, Histidine/analogs & derivatives, Histidine/pharmacology, Humans, Lysophospholipids/biosynthesis, Molecular Structure, Multienzyme Complexes/pharmacology, Neoplasms/metabolism, Neoplasms/pathology, Phosphodiesterase I/pharmacology, Phosphoric Diester Hydrolases/metabolism, Pyrophosphatases/pharmacology, Substrate Specificity, Zinc/chemistry, Zinc/pharmacology |
| الوقت: | 15737239 |
| الوصف: | 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. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1~15 |
| اللغة: | unknown |
| تدمد: | 1476-511X |
| العلاقة: | LIPIDS IN HEALTH AND DISEASE; J02169; OAK-2005-02263; https://ir.ymlib.yonsei.ac.kr/handle/22282913/114985Test; T200505082; LIPIDS IN HEALTH AND DISEASE, Vol.4(5) : 1-15, 2005 |
| DOI: | 10.1186/1476-511X-4-5 |
| الإتاحة: | https://doi.org/10.1186/1476-511X-4-5Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/114985Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ ; free |
| رقم الانضمام: | edsbas.FDF5D6C7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1476511X |
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| DOI: | 10.1186/1476-511X-4-5 |