Coordination Dynamics of Zinc Triggers the Rate Determining Proton Transfer in Human Carbonic Anhydrase II.


Journal

Chemphyschem : a European journal of chemical physics and physical chemistry
ISSN: 1439-7641
Titre abrégé: Chemphyschem
Pays: Germany
ID NLM: 100954211

Informations de publication

Date de publication:
02 07 2020
Historique:
received: 04 03 2020
revised: 17 04 2020
pubmed: 25 4 2020
medline: 26 1 2021
entrez: 25 4 2020
Statut: ppublish

Résumé

We present, for the first time, how transient changes in the coordination number of zinc ion affects the rate determining step in the enzyme human carbonic anhydrase (HCA) II. The latter involves an intramolecular proton transfer between a zinc-bound water and a distant histidine residue (His-64). In the absence of time-resolved experiments, results from classical and QM-MM molecular dynamics and transition path sampling simulations are presented. The catalytic zinc ion is found to be present in two possible coordination states; viz. a stable tetra-coordinated state, T and a less stable penta-coordinated state, P with tetrahedral and trigonal bipyramidal coordination geometries, respectively. A fast dynamical inter-conversion occurs between T and P due to reorganization of active site water molecules making the zinc ion more positively charged in state P. When initiated from different coordination environments, the most probable mechanism of proton transfer is found to be deprotonation of the equatorial water molecule from state P and transfer of the excess proton via a short path formed by hydrogen bonded network of active site water molecules. We estimate the rate constant of proton transfer as

Identifiants

pubmed: 32329944
doi: 10.1002/cphc.202000177
doi:

Substances chimiques

Coordination Complexes 0
Protons 0
Water 059QF0KO0R
Histidine 4QD397987E
Carbonic Anhydrase II EC 4.2.1.-
CA2 protein, human EC 4.2.1.1
Zinc J41CSQ7QDS

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1455-1473

Subventions

Organisme : Science and Engineering Research Board
ID : SR/FST/CSII-011/2005
Pays : International
Organisme : UGC-DAE Consortium for Scientific Research, University Grants Commission
Pays : International

Informations de copyright

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Tanmoy Kumar Paul (TK)

Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302, India.

Srabani Taraphder (S)

Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302, India.

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