Article
Microbiology
An-Qi Li, Wei-Jia Zhang, Xue-Gong Li, Xu-Chong Bao, Xiao-Qing Qi, Long-Fei Wu, Douglas H. Bartlett
Summary: In this study, the deep-sea bacterium Photobacterium profundum SS9 was found to exhibit a more pronounced piezophilic phenotype when grown in minimal medium supplemented with glucose than in a complex medium. The intracellular ATP level varied with pressure, but with opposite trends in the two culture media. The ATPase systems encoded in SS9, ATPase-I and ATPase-II, showed different abundances and functions in response to pressure and culture media.
Article
Chemistry, Multidisciplinary
Shuaiqi Meng, Yu Ji, Luo Liu, Mehdi D. Davari, Ulrich Schwaneberg
Summary: This study demonstrates that engineering the tunnels of cytochrome P450 can improve coupling efficiency by controlling water diffusion. The reduced water molecules around the active site lead to higher coupling efficiency. This research provides valuable insights for improving coupling efficiency through tunnel engineering.
Article
Biochemistry & Molecular Biology
Andre Fischer, Martin Smiesko
Summary: This study investigates an allosteric site in Cytochrome P450 enzymes, finding it to be well conserved in the CYP2 family with the exception of CYP2E1, and observing an enlargement of ligand tunnels in certain members that facilitate ligand translocation. The research contributes to understanding ligand access phenomena and aids in estimating the selectivity of metabolic transformations using computational techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Linda Celeste Montemiglio, Elena Gugole, Ida Freda, Cecile Exertier, Lucia D'Auria, Cheng Giuseppe Chen, Alessandro Nicola Nardi, Gabriele Cerutti, Giacomo Parisi, Marco D'Abramo, Carmelinda Savino, Beatrice Vallone
Summary: This study analyzed the role of a cavity in substrate binding to OleP by mutating its volume. The results showed that inserting bulky residues into the cavity affected the binding properties of the enzyme and perturbed the conformational space of the substrate-enzyme complex. The study highlights the importance of this region in OleP substrate binding and suggests the potential to redirect its activity through this region.
Article
Biotechnology & Applied Microbiology
Bashu Dev Pardhe, Kyoung Pyo Kwon, Jong Kook Park, Jun Hyuck Lee, Tae-Jin Oh
Summary: In this study, CYP105D18 was used as a catalyst for the hydroxylation of steroids with H2O2 as a co-substrate. The hydroxylation positions of different steroids were predicted based on experimental data and molecular docking. Mutations in the substrate access channel were performed to improve substrate conversion. The findings provide a basis for the potential application and further engineering of CYP105D18.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Yohei Iizaka, David H. Sherman, Yojiro Anzai
Summary: Cytochrome P450 enzymes play a significant role in actinomycetes by catalyzing diverse oxidative reactions to produce a variety of compounds such as alcohols, ketones, aldehydes, and carboxylic acids. Understanding the enzymatic properties and reaction mechanisms of these enzymes can facilitate their utilization in biotechnological applications for creating high-value compounds.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Peter Hlavica
Summary: Cytochrome P450s (CYP) are a superfamily of hemoproteins that catalyze the oxidation of a wide range of compounds. This review focuses on the topology of substrate entry and product release channels in mammalian P450s. The hydrophobicity profile plays a significant role in the functional interaction within these channels, while small amino acids act as hinges for conformational flexibility. Narrow bottlenecks and clusters of aromatic amino acids are important for substrate selectivity. Furthermore, peripheral patches in the channels may influence allostery between different parts of the P450 structure. The identified critical residues in these channels could be targeted for genetic engineering to develop more advanced mammalian P450s for industrial, biotechnological, and medicinal applications.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Remigio Usai, Daniel Kaluka, Sheng Cai, Daniel S. Sem, James R. Kincaid
Summary: A new method using heterologous expression of 13C-labeled P450cam was developed to define and refine the solution phase active site structure in cytochrome P450cam.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Microbiology
Vijayakumar Somalinga, Emily Foss, Amy M. Grunden
Summary: This manuscript reports the crystal structure and biochemical characterization of a-CA from Photobacterium profundum SS9. The enzyme showed unusual catalytic properties, including maximal activity at low temperatures, retention of activity at acidic pH, and salt-dependent activity under extreme halophilic conditions.
Review
Chemistry, Multidisciplinary
Dibyendu Mondal, Harrison M. Snodgrass, Christian A. Gomez, Jared C. Lewis
Summary: The ability to selectively modify functional groups in a molecule can simplify syntheses and increase yields. Enzymes can catalyze site-selective transformations, but using this capability for non-native substrates and reactions requires understanding of enzymatic catalysis and protein engineering. This review discusses examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization, focusing on cases with non-native substrates and engineered enzymes. The review also explores the use of these enzymes in chemoenzymatic transformations and target-oriented synthesis, and provides an overview of tools and techniques to expand the scope of non-native site-selective enzyme catalysis.
Article
Biochemistry & Molecular Biology
Srabani Karmakar, Sudip Kumar Nag, Mohd Taher, Bharat T. Kansara, Shyamalava Mazumdar
Summary: This study demonstrates that site-saturation mutation of a single amino acid residue at the substrate binding pocket of thermostable cytochrome P450 can efficiently alter the substrate specificity of the enzyme. Mutations of the tyrosine 68 residue resulted in unique variants with high thermostability and diverse binding and catalytic activities towards different substrates.
Article
Pharmacology & Pharmacy
Shaniece Wauchope, Monika A. Roy, William Irvine, Isaac Morrison, Eileen Brantley, Maxine Gossell-Williams, Alicia R. Timme-Laragy, Rupika Delgoda
Summary: The study demonstrated that dibenzyl trisulfide (DTS) has inhibitory effects on the enzymes CYP1A and CYP1B1, and showed suppression of CYP1A activity in in vivo experiments, with no impact on gene transcription levels. DTS exhibits potential in chemoprevention.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Christopher S. Campomizzi, Amit Kumar, Patil Pranita Uttamrao, Jack J. Stallone, George E. Ghanatios, Thenmalarchelvi Rathinavelan, D. Fernando Estrada
Summary: The essential enzyme CYP121A1 of Mycobacterium tuberculosis forms a functional dimer, disruption of which leads to decreased activity and substrate specificity. Crystal structure analysis reveals that aromatic residues Phe-168 and Trp-182 interact with the substrate cYY mainly through N-N stacking. This study also demonstrates the role of these residues in stabilizing the tertiary and quaternary structures of CYP121A1, and unexpectedly discovers long-range allostery induced by cYY. In summary, this research uncovers the structural relationship between the active site environment and global structure of this essential enzyme.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Kuniaki Mukai, Hiroshi Sugimoto, Katsumasa Kamiya, Reiko Suzuki, Tomomi Matsuura, Takako Hishiki, Hideo Shimada, Yoshitsugu Shiro, Makoto Suematsu, Norio Kagawa
Summary: The study explores the catalytic divergence of human cytochromes P45011 beta and P450(aldo) in synthesizing cortisol and aldosterone. The findings reveal that CYP11B1 functions primarily as an 11 beta-hydroxylase, while CYP11B2 can successively process additional 18-hydroxylations.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wei Lin, Kalyan Das, David Degen, Abhishek Mazumder, Diego Duchi, Dongye Wang, Yon W. Ebright, Richard Y. Ebright, Elena Sineva, Matthew Gigliotti, Aashish Srivastava, Sukhendu Mandal, Yi Jiang, Yu Liu, Ruiheng Yin, Zhening Zhang, Edward T. Eng, Dennis Thomas, Stefano Donadio, Haibo Zhang, Changsheng Zhang, Achillefs N. Kapanidis, Richard H. Ebright
Article
Biochemistry & Molecular Biology
Vadim Molodtsov, Elena Sineva, Lu Zhang, Xuhui Huang, Michael Cashel, Sarah E. Ades, Katsuhiko S. Murakami
Article
Pharmacology & Pharmacy
John T. Rodgers, Nadezhda Y. Davydova, Erickson M. Paragas, Jeffrey P. Jones, Dmitri R. Davydov
BIOCHEMICAL PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Nadezhda Y. Davydova, Bikash Dangi, Marc A. Maldonado, Nikita E. Vavilov, Victor G. Zgoda, Dmitri R. Davydov
BIOCHEMICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Mackenzie E. Gerringer, Paul H. Yancey, Olga V. Tikhonova, Nikita E. Vavilov, Victor G. Zgoda, Dmitri R. Davydov
Article
Plant Sciences
Bixia Zhang, Kevin M. Lewis, Alejandra Abril, Dmitri R. Davydov, Wilfred Vermerris, Scott E. Sattler, ChulHee Kang
Article
Pharmacology & Pharmacy
Bikash Dangi, Nadezhda Y. Davydova, Nikita E. Vavilov, Victor G. Zgoda, Dmitri R. Davydov
Article
Biochemistry & Molecular Biology
Bikash Dangi, Nadezhda Y. Davydova, Marc A. Maldonado, Armina Abbasi, Nikita E. Vavilov, Victor G. Zgoda, Dmitri R. Davydov
Summary: The study found that the increase in CYP2E1 content significantly affects the metabolism rate of certain substrates and weakens homotropic cooperativity. Chronic alcohol exposure may impact the pharmacokinetics of drugs metabolized by CYP3A4.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Bikash Dangi, Nadezhda Y. Davydova, Marc A. Maldonado, Deepak Ahire, Bhagwat Prasad, Dmitri R. Davydov
Summary: This study investigated the relationship between drug metabolism routes and the composition of the P450 ensemble in human liver microsomes. The results showed that CYP2B6 and CYP3A5 play a crucial role in C152 metabolism. Analysis using PCA revealed significant differences between HLM samples, highlighting the pivotal role of P450-P450 interactions in determining drug metabolism routes.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Editorial Material
Biology
Dmitri R. Davydov, Christiane Jung, Gregory A. Petsko, Stephen G. Sligar, Jack A. Kornblatt
Article
Biochemistry & Molecular Biology
Dmitri R. Davydov, Bikash Dangi, Guihua Yue, Deepak S. Ahire, Bhagwat Prasad, Victor G. Zgoda
Summary: This study used chemical crosslinking mass spectrometry (CXMS) to explore the protein-protein interactions of alcohol-induced cytochrome P450 2E1 (CYP2E1) in human liver microsomes. By analyzing the crosslinked complexes, it was found that CYP2E1 is tightly integrated with other drug-metabolizing enzymes through protein-protein interactions.
Article
Plant Sciences
Supratim Basu, Elena Sineva, Liza Nguyen, Narattam Sikdar, Jong Won Park, Mikhail Sinev, Madhurababu Kunta, Goutam Gupta
Summary: This article introduces a novel therapy for citrus Huanglongbing (HLB) and apple fire blight by enhancing the innate immunity of the host plants. The researchers constructed chimeras with observed or predicted antibacterial activity and demonstrated their effectiveness in clearing the causative bacteria and augmenting the host's immune response.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biology
Nadezhda Y. Davydova, David A. Hutner, Kari A. Gaither, Dilip Kumar Singh, Bhagwat Prasad, Dmitri R. Davydov
Summary: In this study, a reliable, inexpensive, and versatile method for high-throughput kinetic assays of drug metabolism based on fluorometric quantification of formaldehyde (FA) was introduced. The method was applied for automatized assays of cytochrome P450-dependent drug metabolism in human liver microsomes and was used to re-evaluate the metabolism pathways of ketamine. By probing the kinetic parameters of ketamine demethylation by ten major cytochrome P450 (CYP) enzymes, it was found that CYP2B6, CYP3A, CYP2C19, and CYP2D6 play important roles in ketamine metabolism, while the involvement of CYP2C9 was deemed insignificant.
Meeting Abstract
Zoology
M. E. Gerringer, P. H. Yancey, O. Tikhonova, N. E. Vavvlov, V. G. Zgoda, D. R. Davydov
INTEGRATIVE AND COMPARATIVE BIOLOGY
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Dmitri R. Davydov