Structural studies of BmooMPα-I, a non-hemorrhagic metalloproteinase from Bothrops moojeni venom
Structural studies of BmooMPα-I, a non-hemorrhagic metalloproteinase from Bothrops moojeni venom
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DOI：
10.1016/j.toxicon.2009.08.013
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发表时间：
2010-02-01
期刊：
影响因子：
2.8
通讯作者：
Murakami, M. T.
中科院分区：
文献类型：
--
作者：
Akao, P. K.;Tonoli, C. C. C.;Murakami, M. T.
具有止血活性的蛇毒金属蛋白酶（SVMPs）在特定的点扰乱凝血级联，由于其作为溶栓剂的潜在应用，溶解纤维蛋白（原）的非出血性SVMPs已被用作凝血研究和诊断的生化工具。结构研究与金属蛋白酶抑制剂的设计相辅相成，有助于了解它们的立体特异性和作用机制。我们在这里展示了BmooMP α - 1晶体结构的细节，BmooMP α - 1是一种22.6 kDa的非出血性p - 1类SVMP，从Bothrops moojeni毒液中分离出来，以1.76埃分辨率测定。在这个结构中，催化锌离子表现出不同寻常的八面体配位，由三个典型的组氨酸(His（142), His（146）和His(152)）以及三个溶剂分子组成。比较序列和结构研究表明，由153-164和167-176氨基酸段组成的基序与蛋氨酸转位相邻，是区分非和出血性P-I类svmp的显著特征，并可能直接参与出血性P-I类svmp的发展。2009爱思唯尔有限公司版权所有。
Hemostatically active snake venom metalloproteinases (SVMPs) perturb the blood coagulation cascade at specific points and due to their potential application as thrombolytic agents, the fibrin(ogen)olytic non-hemorrhagic SVMPs have been employed as biochemical tools in coagulation research and diagnosis. Structural studies complemented by the design of metalloproteinase inhibitors have been instrumental in understanding their stereo specificity and action mechanism. We present here, details of the crystal structure of BmooMP alpha-I, a 22.6 kDa non-hemorrhagic P-I class SVMP isolated from Bothrops moojeni venom, determined at 1.76 angstrom resolution. In this structure, the catalytic zinc ion displays an unusual octahedral coordination formed by the three canonical histiclines (His(142), HiS(146) and His(152)) and additionally, by three solvent molecules. Comparative sequence and structural studies indicate that the motif comprising amino acid segments 153-164 and 167-176 adjacent to the methionine-turn is a salient feature that differentiates both non and hemorrhagic P-I class SVMPs and could directly be involved in the development of the hemorrhagic activity. (C) 2009 Elsevier Ltd. All rights reserved.