دورية أكاديمية
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Influence of the Greater Protein Environment on the Electrostatic Potential in Metalloenzyme Active Sites: The Case of Formate Dehydrogenase.

التفاصيل البيبلوغرافية
العنوان: Influence of the Greater Protein Environment on the Electrostatic Potential in Metalloenzyme Active Sites: The Case of Formate Dehydrogenase.
المؤلفون: Nazemi A; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Steeves AH; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Kastner DW; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Kulik HJ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
المصدر: The journal of physical chemistry. B [J Phys Chem B] 2022 Jun 09; Vol. 126 (22), pp. 4069-4079. Date of Electronic Publication: 2022 May 24.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c1997-
مواضيع طبية MeSH: Formate Dehydrogenases*/chemistry , Metalloproteins*/chemistry, Catalytic Domain ; Ligands ; Static Electricity
مستخلص: The Mo/W-containing metalloenzyme formate dehydrogenase (FDH) is an efficient and selective natural catalyst that reversibly converts CO 2 to formate under ambient conditions. In this study, we investigate the impact of the greater protein environment on the electrostatic potential (ESP) of the active site. To model the enzyme environment, we used a combination of classical molecular dynamics and multiscale quantum-mechanical (QM)/molecular-mechanical (MM) simulations. We leverage charge shift analysis to systematically construct QM regions and analyze the electronic environment of the active site by evaluating the degree of charge transfer between the core active site and the protein environment. The contribution of the terminal chalcogen ligand to the ESP of the metal center is substantial and dependent on the chalcogen identity, with similar, less negative ESPs for Se and S terminal chalcogens in comparison to O regardless of whether the metal is Mo or W. The orientation of the side chains and conformations of the cofactor also affect the ESP, highlighting the importance of sampling dynamic fluctuations in the protein. Overall, our observations suggest that the terminal chalcogen ligand identity plays an important role in the enzymatic activity of FDH, suggesting opportunities for a rational bioinspired catalyst design.
المشرفين على المادة: 0 (Ligands)
0 (Metalloproteins)
EC 1.17.1.9 (Formate Dehydrogenases)
تواريخ الأحداث: Date Created: 20220524 Date Completed: 20220610 Latest Revision: 20220717
رمز التحديث: 20240628
DOI: 10.1021/acs.jpcb.2c02260
PMID: 35609244
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5207
DOI:10.1021/acs.jpcb.2c02260