Determinants of cysteine pKa values in creatine kinase and α1‐antitrypsin
- 8 October 2004
- journal article
- Published by Wiley in Proteins-Structure Function and Bioinformatics
- Vol. 57 (4) , 799-803
- https://doi.org/10.1002/prot.20261
Abstract
The structural determinants of the unusually low pKa values of Cys282 in human creatine kinase and Cys232 in α1‐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 α1‐antitrypsin the donor is an amide NH. Each hydrogen bond lowers the pKa 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 pKa value of wild‐type and the S284A mutant of creatine kinase. Proteins 2004.Keywords
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