Journal Article

FZJ-2021-03307

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png F/G Region Rigidity is Inversely Correlated to Substrate Promiscuity of Human CYP Isoforms Involved in Metabolism

Becker, D. ; Bharatam, P. V. ; Gohlke, H. (Corresponding author)FZJ*

2021
American Chemical Society Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/28569  doi:10.1021/acs.jcim.1c00558

Abstract: Of 57 human cytochrome P450 (CYP) enzymes, 12 metabolize 90% of xenobiotics. To our knowledge, no study has addressed the relation between enzyme dynamics and substrate promiscuity for more than three CYPs. Here, we show by constraint dilution simulations with the Constraint Network Analysis for the 12 isoforms that structural rigidity of the F/G region is significantly inversely correlated to the enzymes’ substrate promiscuity. This highlights the functional importance of structural dynamics of the substrate tunnel.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. John von Neumann - Institut für Computing (NIC)
3. Strukturbiochemie (IBI-7)
4. Bioinformatik (IBG-4)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
3. 2172 - Utilization of renewable carbon and energy sources and engineering of ecosystem functions (POF4-217) (POF4-217)
4. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)

Appears in the scientific report 2021

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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