From random to rational: improving enzyme design through electric fields, second coordination sphere interactions, and conformational dynamics

SS Chaturvedi, D Bím, CZ Christov… - Chemical Science, 2023 - pubs.rsc.org
Enzymes are versatile and efficient biological catalysts that drive numerous cellular
processes, motivating the development of enzyme design approaches to tailor catalysts for …

DNA replicases from a bacterial perspective

CS McHenry - Annual review of biochemistry, 2011 - annualreviews.org
Bacterial replicases are complex, tripartite replicative machines. They contain a polymerase,
polymerase III (Pol III), a β2 processivity factor, and a DnaX complex ATPase that loads β2 …

Principles of target DNA cleavage and the role of Mg2+ in the catalysis of CRISPR–Cas9

Ł Nierzwicki, KW East, JM Binz, RV Hsu, M Ahsan… - Nature …, 2022 - nature.com
At the core of the CRISPR–Cas9 genome-editing technology, the endonuclease Cas9
introduces site-specific breaks in DNA. However, precise mechanistic information to …

Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed by Ab Initio Molecular Dynamics

L Casalino, Ł Nierzwicki, M **ek, G Palermo - ACS catalysis, 2020 - ACS Publications
CRISPR-Cas9 is a cutting-edge genome editing technology, which uses the endonuclease
Cas9 to introduce mutations at desired sites of the genome. This revolutionary tool is …

Cap binding and immune evasion revealed by Lassa nucleoprotein structure

X Qi, S Lan, W Wang, LML Schelde, H Dong, GD Wallat… - Nature, 2010 - nature.com
Lassa virus, the causative agent of Lassa fever, causes thousands of deaths annually and is
a biological threat agent, for which there is no vaccine and limited therapy. The …

Can second coordination sphere and long-range interactions modulate hydrogen atom transfer in a non-heme Fe (II)-dependent histone demethylase?

SS Chaturvedi, SB Jaber Sathik Rifayee, SO Waheed… - JACS Au, 2022 - ACS Publications
Fe (II)-dependent oxygenases employ hydrogen atom transfer (HAT) to produce a myriad of
products. Understanding how such enzymes use dynamic processes beyond the immediate …

Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations

E Rosta, M Nowotny, W Yang… - Journal of the American …, 2011 - ACS Publications
We use quantum mechanics/molecular mechanics simulations to study the cleavage of the
ribonucleic acid (RNA) backbone catalyzed by ribonuclease H. This protein is a prototypical …

How human TET2 enzyme catalyzes the oxidation of unnatural cytosine modifications in double-stranded DNA

SO Waheed, A Varghese, SS Chaturvedi… - ACS …, 2022 - ACS Publications
Methylation of cytosine bases is strongly linked to gene expression, imprinting, aging, and
carcinogenesis. The ten-eleven translocation (TET) family of enzymes, which are Fe (II)/2 …

Atomic and Electronic Structure Determinants Distinguish between Ethylene Formation and l-Arginine Hydroxylation Reaction Mechanisms in the Ethylene-Forming …

SS Chaturvedi, R Ramanan, J Hu, RP Hausinger… - ACS …, 2021 - ACS Publications
The ethylene-forming enzyme (EFE) is a non-heme Fe (II), 2-oxoglutarate (2OG), and l-
arginine (l-Arg)-dependent oxygenase that catalyzes dual reactions: the generation of …

Computational characterization of the inhibition mechanism of xanthine oxidoreductase by topiroxostat

Y Maghsoud, C Dong, GA Cisneros - ACS catalysis, 2023 - ACS Publications
Xanthine oxidase (XO) is a member of the molybdopterin-containing enzyme family. It
interconverts xanthine to uric acid as the last step of purine catabolism in the human body …