Role of Thr199 residue in human β-carbonic anhydrase-II pH-dependent activity elucidated by microsecond simulation analysis

Yadav, Pulala Raghuveer and Basha, Syed Hussain and Pindi, Pavan Kumar (2022) Role of Thr199 residue in human β-carbonic anhydrase-II pH-dependent activity elucidated by microsecond simulation analysis. Journal of Biomolecular Structure and Dynamics, 40 (11). pp. 5016-5025. ISSN 0739-1102

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Abstract

Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions such as carbon assimilation, pH acid–base homeostasis, respiration and photosynthesis via a zinc-hydroxide mechanism for carbon dioxide hydration. In earlier studies, it was revealed that Carbonic anhydrases are inactive at pH 7.5 and active at pH 8.4. This steep pH dependence for its activity led us to design this work to understand its mode of action at atomic level detail. In our microsecond simulation based analysis, it was revealed that the interaction between Glu106 and Thr199 plays a critically important role in its activity. Thr199 co-ordinated loop movement was observed to be acting as a lid, with ‘open’ and ‘close’ mechanism for substrate entry to the core of the catalytic site, where Zn-ion resides and executes its carbon dioxide hydration mechanism. On the other hand, decline in the total secondary structural elements percentage in the protein was observed in correspondence to the pH condition change. The α-helices between Thr125-Gly145 and Val150-Lys170 residues were especially noticed to be losing their structural integrity responsible for formation of dimer and tetramers. In conclusion, our analysis showed that the interaction between Glu106 and Thr199 is crucial for maintaining the structural integrity of the Thr199 coordinated loop, responsible for allowing substrate towards the catalytic site. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

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Item Type: Article
Uncontrolled Keywords: carbon dioxide hydration; Glu106 and Thr199 interaction; Human β-carbonic anhydrase-II; molecular dynamic simulations; pH dependent activity
Subjects: Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: . LibTrainee 2021
Date Deposited: 17 Oct 2022 04:27
Last Modified: 17 Oct 2022 04:27
URI: http://raiith.iith.ac.in/id/eprint/10967
Publisher URL: http://doi.org/10.1080/07391102.2020.1865203
OA policy: https://v2.sherpa.ac.uk/id/publication/23484
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