Article
Chemistry, Multidisciplinary
Beatrice Battistella, Thomas Lohmiller, Beatrice Cula, Peter Hildebrandt, Uwe Kuhlmann, Holger Dau, Stefan Mebs, Kallol Ray
Summary: In class Ib ribonucleotide reductases (RNRs), a dimanganese(II) cluster activates superoxide (O-2(center dot-)) to form a high valent Mn-III-O-2-Mn-IV species responsible for the oxidation of tyrosine. A thiolate-bound dimanganese complex [Mn-2(II)(BPMT)(OAc)(2)](ClO)(4) was synthesized as a biomimetic model for RNRs and proved to be a capable oxidant in aldehyde deformylation and phenol oxidation reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Microbiology
Kwang-Woo Jung, Sunhak Kwon, Jong-Hyun Jung, Yong-Sun Bahn
Summary: The regulation of RNR genes has conserved and divergent features in C. neoformans during DNA replication and DNA damage stress, compared with other yeasts.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biology
Sofia N. Moraes, Jordan T. Becker, Seyed Arad Moghadasi, Nadine M. Shaban, Ashley A. Auerbach, Adam Z. Cheng, Reuben S. Harris
Summary: Viruses have evolved mechanisms to counteract host immunity, including inhibiting and relocalizing cellular APOBEC3B (A3B) through the ribonucleotide reductase (RNR) of Epstein-Barr virus. This study investigates the conserved mechanisms and evolutionary origin of this immune counteraction strategy. The results show that human gamma-herpesvirus RNRs interact with A3B through distinct surfaces and their enzymatic inhibition and relocalization of A3B depend on binding to different regions of the catalytic domain. Additionally, the ability of viral RNRs to counteract A3B is conserved in gamma-herpesviruses that infect humans and Old World monkeys but absent in homologous viruses that infect New World monkeys.
Article
Chemistry, Medicinal
Felipe Curtolo, Guilherme M. Arantes
Summary: The interconversion between fumarate and succinate is vital for energy metabolism in organisms and is catalyzed by fumarate reductases and succinate dehydrogenases. These flavoenzymes play important roles in biomedical and biotechnological fields. The understanding of their catalytic mechanisms is valuable for further research and applications.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
A. M. U. B. Mahfuz, Muhammad Nasir Iqbal, Felipe Stambuk Opazo, A. M. Zubair-Bin-Mahfuj
Summary: Antibiotic resistance is a global concern, with Elizabethkingia species like E. anophelis and E. meningoseptica being resistant to multiple antibiotics. Researchers are exploring new antibiotics that target unconventional sites, such as bacterial ribonucleotide reductases. This study evaluates the binding affinities of compounds inhibiting Pseudomonas aeruginosa growth by targeting its ribonucleotide reductase with enzymes from E. anophelis and E. meningoseptica to combat infections in the future.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Microbiology
Chee-Hing Yang, Cheng-Hao Wu, Shih-Yen Lo, Ahai-Chang Lua, Yu-Ru Chan, Hui-Chun Li
Summary: The expression of cellular RRMs is down-regulated in HCV-infected cells, leading to an increased NTP/dNTP ratio and enhanced HCV replication. NS5A and/or NS3/4A proteins suppress the expression of RRMs.
Review
Chemistry, Physical
Kai Wu, Junhai Huang, Lei Shao
Summary: The synthesis of chiral amines is important in the pharmaceutical industry. IRED, a promising biocatalyst, has been found to catalyze direct asymmetric reductive amination and conjugate reduction, producing valuable amine diastereomers. This review provides insights into the catalytic mechanisms of IREDs and highlights their potential for industrial applications.
Article
Chemistry, Multidisciplinary
Nabhendu Pal, Manish Jana, Amit Majumdar
Summary: Reduction of nitric oxide to nitrous oxide is crucial for biological and health implications, with FNORs playing a key role in catalyzing this reaction. Various mechanisms have been proposed for the catalytic NO reduction by FNORs, and model studies have greatly helped in understanding the mechanism.
CHEMICAL COMMUNICATIONS
(2021)
Article
Plant Sciences
Huanying Li, Lin Li, Weichen Wu, Fei Wang, Fei Zhou, Yongjun Lin
Summary: This study investigated the role of ribonucleotide reductases in plants, identifying a key gene SvSTL1 involved in chloroplast development and demonstrating its essential function in RNRs. Through generation of mutants using CRISPR/Cas9 technology, it was found that different RNR large subunit genes affect the copy number of chloroplast genome and chloroplast development.
Review
Microbiology
Fernanda S. M. Hopf, Candida D. Roth, Eduardo V. de Souza, Luiza Galina, Alexia M. Czeczot, Pablo Machado, Luiz A. Basso, Cristiano V. Bizarro
Summary: This article reviews the diversity, structure, and catalytic properties of enoyl-ACP reductases (ENRs) and their potential as drug development targets. It also discusses the complex evolutionary history of bacterial ENRs.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Dermatology
Ahmed A. Hawash, Giuseppe Ingrasci, Keyvan Nouri, Gil Yosipovitch
Summary: Keloids are scars that extend beyond the margins of an insulting cutaneous injury, causing functional symptoms such as pruritus and pain, in addition to being a cosmetic issue. Pruritus symptom is often overlooked by dermatologists, with treatments primarily focusing on the scar's appearance. Various treatments targeting itch and emerging therapies have been described in this review.
ACTA DERMATO-VENEREOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Yaohui Li, Rongzhen Zhang, Yan Xu
Summary: This study summarizes the structures and behaviors of alcohol dehydrogenases/reductases in organic-aqueous systems, comparing the structures of enzymes with different tolerance towards organic solvents. By understanding the catalytic mechanisms of these enzymes in organic-aqueous systems, the efficient enantioselective syntheses mediated by alcohol dehydrogenases/reductases and further challenges are discussed through solvent engineering and enzyme immobilization in the last decade.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Samuel L. Rose, Seiki Baba, Hideo Okumura, Svetlana Antonyuk, Daisuke Sasaki, Tobias M. Hedison, Muralidharan Shanmugam, Derren J. Heyes, Nigel S. Scrutton, Takashi Kumasaka, Takehiko Tosha, Robert R. Eady, Masaki Yamamoto, S. Samar Hasnain
Summary: Redox reactions play a crucial role in substrate binding and utilization in enzyme catalysis. A recent study found that a CuNiR with lower catalytic activity had its catalytic site occupied by water molecules. The study showed that there was less inter-Cu electron transfer in the presence of nitrite, which may explain the lower activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Critical Care Medicine
David F. Condon, Stuti Agarwal, Ananya Chakraborty, Natasha Auer, Rocio Vazquez, Hirai Patel, Roham T. Zamanian, Vinicio A. de Jesus Perez
Summary: Pulmonary arterial hypertension (PAH) is a rare disease characterized by abnormally elevated pulmonary pressures and right heart failure, resulting in high morbidity and mortality. Current therapies are insufficient in preventing small-vessel loss and obstruction, leading to active interest in identifying drugs that target angiogenesis and mechanisms involved in cell growth and fibrosis regulation. Preclinical studies have identified promising compounds that target seven major mechanisms associated with PAH pathogenesis, including bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. This review discusses the prioritization of these mechanisms through preclinical studies, as well as ongoing clinical trials testing novel interventions. The authors anticipate that the next generation of compounds will build upon the current standard of care and improve clinical outcomes and quality of life for PAH patients.
Article
Biochemistry & Molecular Biology
Maria Luiza Caldas Nogueira, Anthony J. Pastore, Victor L. Davidson
Summary: Oxo-bridged diiron proteins are a unique class of non-heme iron proteins with active sites composed of two iron atoms and a bridging oxygen. They share a four alpha-helix bundle structure and exhibit a wide range of structures and functions, including hemerythrin and rubrerythrin-like proteins. These proteins also include oxo-bridged irons in enzymes such as flavodiiron proteins and ferritins.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Lisa Olshansky, Brandon L. Greene, Chelsea Finkbeiner, JoAnne Stubbe, Daniel G. Nocera
Article
Biochemistry & Molecular Biology
Brandon L. Greene, Chang-Hao Wu, Gregory E. Vansuch, Michael W. W. Adams, R. Brian Dyer
Article
Chemistry, Multidisciplinary
Brandon L. Greene, Alexander T. Taguchi, JoAnne Stubbe, Daniel G. Nocera
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Chemistry, Physical
Brandon L. Greene, Gerrit J. Schut, Michael W. W. Adams, R. Brian Dyer
Article
Chemistry, Multidisciplinary
Brandon L. Greene, JoAnne Stubbe, Daniel G. Nocera
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Article
Biochemistry & Molecular Biology
Brandon L. Greene, JoAnne Stubbe, Daniel G. Nocera
Article
Chemistry, Multidisciplinary
Chang Cui, Brandon L. Greene, Gyunghoon Kang, Catherine L. Drennan, JoAnne Stubbe, Daniel G. Nocera
Summary: This study reveals that the oxidation of Y-356 in E. coli ribonucleotide reductase is regulated by a specific residue, E-52, which facilitates proton transfer through a water channel at the subunit interface. The E(52)Q variant is unable to oxidize Y-356, indicating the essential role of E-52 in proton management.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Brandon L. Greene
Summary: Strategies inspired by photosynthesis have been applied to rapidly initiate oxidoreductase catalysis for mechanistic investigations, providing important contributions to the understanding of hydrogenases and artificially photosynthetic ribonucleotide reductases. The potential for application in other oxidoreductases is also discussed in this Perspective.
Article
Chemistry, Multidisciplinary
Chang Cui, David Y. Song, Catherine L. Drennan, JoAnne Stubbe, Daniel G. Nocera
Summary: Ribonucleotide reductases (RNRs) are pivotal in converting nucleotides in all organisms. The Escherichia coli class Ia RNR consists of two subunits, alpha and beta, forming an asymmetric alpha alpha 'beta beta ' complex. The reactions involve a proton-coupled electron transfer pathway, in which key residues E52[beta], R331[alpha], E326[alpha], and E326[alpha '] play a crucial role. Mutagenesis studies and photochemical assays provide further insights into the mechanism of proton transfer associated with Y356 oxidation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Juan Carlos Caceres, August Dolmatch, Brandon L. Greene
Summary: This study reveals the mechanism of inhibition of pyruvate formate lyase (PFL) by methacrylate. It is found that treatment of activated PFL with methacrylate leads to the conversion of the G(734)center dot to a C2 tertiary methacryl radical, accompanied by enzyme inhibition. The two active site cysteines of PFL are found to play unique roles.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Analytical
Clara A. Bailey, Brandon L. Greene
Summary: Phosphite is an important metabolite in phosphorus cycle and has unique agricultural properties. The accurate and selective detection of phosphite is crucial for studying phosphorus redox chemistry. In this study, a fluorescence-based assay using phosphite dehydrogenase and resazurin was developed for rapid and accurate phosphite quantification. The assay can detect phosphite with a limit of detection of 3 μM in various biologically- and environmentally-relevant samples, and was used to demonstrate phosphite uptake in a model crop plant and the efficiency of a phosphite converting biofertilizer.
Review
Chemistry, Multidisciplinary
Brandon L. Greene, Gregory E. Vansuch, Bryant C. Chica, Michael W. W. Adams, R. Brian Dyer
ACCOUNTS OF CHEMICAL RESEARCH
(2017)