Determinants of cysteine pKa values in creatine kinase and α1-antitrypsin
Determinants of cysteine pKa values in creatine kinase and α1-antitrypsin
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DOI：
10.1002/prot.20261
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发表时间：
2004-12-01
影响因子：
2.9
通讯作者：
Jensen, JH
中科院分区：
文献类型：
--
作者：
Naor, MM;Jensen, JH
计算研究了人肌酸激酶中Cys 282和α 1-抗胰蛋白酶中Cys 232的pK（a）值异常低的结构决定因素。我们已经证明，氢键的半胱氨酸残基是这两种蛋白质的主要决定因素。在肌酸激酶的情况下，氢键供体是丝氨酸侧链和酰胺NH-基团，而在α 1-抗胰蛋白酶中，供体是酰胺NH。每个氢键使pK（alpha）降低0.8至1.5个pH单位。由于Ser 284-Cys 282氢键导致的1.1单位降低与肌酸激酶的野生型和S284 A突变体的Cys 282 pK（α）值之间的1.2单位差异非常一致。(C)2004 Wiley-Liss，Inc.
The structural determinants of the unusually low pK(a) values of Cys282 in human creatine kinase and Cys232 in alpha1-antitrypsin were studied computationally. We have demonstrated that hydrogen bonding to the cysteine residue is the prime determinant for both proteins. In the case of creatine kinase, the hydrogen bond donors are a serine side chain and an amide NH-group, while in alpha1-antitrypsin the donor is an amide NH. Each hydrogen bond lowers the pK(alpha) by between 0.8 and 1.5 pH units. The 1.1-unit lowering due to the Ser284-Cys282 hydrogen bond is in good agreement with the 1.2-unit difference between the Cys282 pK(alpha) value of wild-type and the S284A mutant of creatine kinase. (C) 2004 Wiley-Liss, Inc.