THE ACTIVE-SITE OF ASPARTIC PROTEINASES
THE ACTIVE-SITE OF ASPARTIC PROTEINASES
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DOI：
10.1016/0014-5793(84)81085-6
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发表时间：
1984-01-01
期刊：
影响因子：
3.5
通讯作者：
BLUNDELL, T
中科院分区：
文献类型：
--
作者：
PEARL, L;BLUNDELL, T
用X-射线分析确定了天冬氨酸蛋白酶的活性部位--内皮肽酶，并用最小二乘法对其进行了限制最小二乘求精，其晶体一致性为0.16。这两个具有重要催化作用的天冬氨酸基团的环境非常相似，NH2-和COOH-末端结构域对催化中心的贡献通过一个局部2重轴联系在一起。天冬氨酸的羧酸盐共享一个氢键，并与位于局部二聚体上的结合水分子或氢离子具有同等的接触。32和215附近的主链通过一种新的相互作用连接在一起，这种相互作用涉及二联体相关的苏氨酸。结果表明，天门冬氨酸活性中心的两个pKa_1值与顺丁烯二酸中具有氢键中间体和二元酸的结构相似，其特征是两个负电荷基团之间存在静电排斥。
The active site of the aspartic proteinase, endothiapepsin, has been defined by X‐ray analysis and restrained least‐squares refinement at 2.1 Å resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH2‐ and COOH‐terminal domains to the catalytic centre are related by a local 2‐fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad‐related threonines. It is suggested that the two pKa, values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen‐bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups.