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Exploring the Molecular Origins of Protein Dynamics in the Active Site of Human Carbonic Anhydrase II
Journal article   Peer reviewed

Exploring the Molecular Origins of Protein Dynamics in the Active Site of Human Carbonic Anhydrase II

Sarah E Hill, Jigar N Bandaria, Michelle Fox, Elizabeth Vanderah, Amnon Kohen and Christopher M Cheatum
The journal of physical chemistry. B, Vol.113(33), pp.11505-11510
08/20/2009
DOI: 10.1021/jp901321m
PMCID: PMC2736349
PMID: 19637848

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Abstract

We present three-pulse vibrational echo measurements of azide ion bound to the active site Zn of human carbonic anhydrase II (HCA II) and of two separate active-site mutants Thr199 →Ala (T199A) and Leu198 →Phe (L198F). Because structural motions of the protein active site influence the frequency of bound ligands, the differences in the time scales of the frequency-frequency correlation functions (FFCFs) obtained from global fits to each set of data allow us to make inferences about the time scales of the active site dynamics of HCA II. Surprisingly, the deletion of a potential electrostatic interaction in T199A results in very little change in the FFCF, but the insertion of the bulky phenylalanine ring in L198F causes much faster dynamics. We conclude that the fast, sub-picosecond time scale in the correlation function is attributable to hydrogen bond dynamics, and the slow, apparently static contribution is due to the conformational flexibility of Zn-bound azide in the active site. © 2009 American Chemical Society.

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