Computational prediction of metabolism: sites, products, SAR, P450 enzyme dynamics, and mechanisms

J Kirchmair, MJ Williamson, JD Tyzack… - Journal of chemical …, 2012 - ACS Publications
Metabolism of xenobiotics remains a central challenge for the discovery and development of
drugs, cosmetics, nutritional supplements, and agrochemicals. Metabolic transformations …

A novel type of allosteric regulation: functional cooperativity in monomeric proteins

IG Denisov, SG Sligar - Archives of biochemistry and biophysics, 2012 - Elsevier
Cooperative functional properties and allosteric regulation in cytochromes P450 play an
important role in xenobiotic metabolism and define one of the main mechanisms of drug …

Site-specific 1D and 2D IR spectroscopy to characterize the conformations and dynamics of protein molecular recognition

S Ramos, MC Thielges - The Journal of Physical Chemistry B, 2019 - ACS Publications
Proteins exist as ensembles of interconverting states on a complex energy landscape. A
complete, molecular-level understanding of their function requires knowledge of the …

Detection of substrate-dependent conformational changes in the P450 fold by nuclear magnetic resonance

AM Colthart, DR Tietz, Y Ni, JL Friedman, M Dang… - Scientific reports, 2016 - nature.com
Cytochrome P450 monooxygenases typically catalyze the insertion of one atom of oxygen
from O2 into unactivated carbon-hydrogen and carbon-carbon bonds, with concomitant …

Tracking protein–protein interactions by NMR: conformational selection in human steroidogenic cytochrome P450 CYP17A1 induced by cytochrome b 5

AM Richard, DF Estrada, L Flynn… - Physical Chemistry …, 2024 - pubs.rsc.org
The human steroidogenic cytochrome P450 CYP17A1 catalyzes two types of reactions in
the biosynthetic pathway leading from pregnenolone to testosterone and several other …

What your crystal structure will not tell you about enzyme function

TC Pochapsky, SS Pochapsky - Accounts of chemical research, 2019 - ACS Publications
Conspectus Enzyme function requires that enzyme structures be dynamic. Substrate
binding, product release, and transition state stabilization typically involve different enzyme …

Carbon monoxide poisoning is prevented by the energy costs of conformational changes in gas-binding haemproteins

SV Antonyuk, N Rustage, CA Petersen, JL Arnst… - Proceedings of the …, 2011 - pnas.org
Carbon monoxide (CO) is a product of haem metabolism and organisms must evolve
strategies to prevent endogenous CO poisoning of haemoproteins. We show that energy …

A dynamic understanding of cytochrome P450 structure and function through solution NMR

TC Pochapsky - Current opinion in biotechnology, 2021 - Elsevier
Many economically important biosyntheses incorporate regiospecific and stereospecific
oxidations at unactivated carbons. Such oxidations are commonly catalyzed by cytochrome …

Conformational heterogeneity and the affinity of substrate molecular recognition by cytochrome P450cam

EJ Basom, BA Manifold, MC Thielges - Biochemistry, 2017 - ACS Publications
The broad and variable substrate specificity of cytochrome P450 enzymes makes them a
model system for studying the determinants of protein molecular recognition. The archetypal …

Conformational heterogeneity suggests multiple substrate binding modes in CYP106A2

NR Wong, R Sundar, S Kazanis, J Biswas… - Journal of inorganic …, 2023 - Elsevier
Abstract CYP106A2 (cytochrome P450 meg) is a bacterial enzyme originally isolated from B.
megaterium, and has been shown to hydroxylate a wide variety of substrates, including …