Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: A homologue of human PSA
Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: A homologue of human PSA
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DOI：
10.1016/s0022-2836(02)00705-2
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发表时间：
2002-09-13
影响因子：
5.6
通讯作者：
Romao, MJ
中科院分区：
文献类型：
--
作者：
Carvalho, AL;Sanz, L;Romao, MJ
前列腺特异性激肽释放酶是丝氨酸蛋白酶基因家族的一员，最初在精液中发现，是前列腺癌诊断和预后最有用的血清标志物。报道了马前列腺激肽释放酶(HPK)1.42埃分辨率的晶体结构。这是从精浆中提纯的丝氨酸蛋白酶的第一个结构。HPK与人类前列腺特异性抗原(PSA)有广泛的序列同源性，包括预测的胰凝乳酶样特异性，这表明在特异性口袋的S1位置存在丝氨酸残基。与其他激肽释放酶不同，HPK在结构上显示出明显的特异性口袋。它的入口被激肽释放酶环阻断，这表明该环可能起到保护或底物选择的作用。HPK结构似乎处于失活状态，可能需要进一步处理才能与底物分子结合。晶体浸泡实验揭示了已知的两种PSA抑制剂--锌和汞的结合部位。(C)2002爱思唯尔科学有限公司。保留所有权利
Prostate-specific kallikrein, a member of the gene family of serine proteases, was initially discovered in semen and is the most useful serum marker for prostate cancer diagnosis and prognosis. We report the crystal structure at 1.42 Angstrom resolution of horse prostate kallikrein (HPK). This is the first structure of a serine protease purified from seminal plasma. HPK shares extensive sequence homology with human prostate-specific antigen (PSA), including a predicted chymotrypsin-like specificity, as suggested by the presence of a serine residue at position S1 of the specificity pocket. In contrast to other kallikreins, HPK shows a structurally distinct specificity pocket. Its entrance is blocked by the kallikrein loop, suggesting a possible protective or substrate-selective role for this loop. The HPK structure seems to be in an inactivated state and further processing might be required to allow the binding of substrate molecules. Crystal soaking experiments revealed a binding site for Zn2+ and Hg2+, two known PSA inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved