Article
Biochemistry & Molecular Biology
Juan Huang, Qin Xu, Zhuo Liu, Nitin Jain, Madhusudan Tyagi, Dong-Qing Wei, Liang Hong
Summary: This study found that the high density of salt bridges in CYP450 proteins reduces structural flexibility, affecting substrate selection and catalytic activity. By making slight chemical changes, the CYP450 superfamily can regulate the structural flexibility of its member proteins to differentiate substrate specificities.
Article
Chemistry, Physical
F. Peter Guengerich, Stella A. Child, Ian R. Barckhausen, Margo H. Goldfarb
Summary: The bacterial cytochrome P450(cam) binds its substrate camphor through an induced-fit mechanism, where the enzyme changes conformation after binding the substrate. This behavior is different from other P450 enzymes that utilize a conformational selection process for substrate recognition. The accessory protein putidaredoxin has no effect on substrate binding, indicating a unique mechanism for substrate recognition by P450(cam).
Article
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Meghan E. Davies, Daniel Tsyplenkov, Vincent J. J. Martin
Summary: This study demonstrates for the first time de novo synthesis of nepetalactone in Saccharomyces cerevisiae, overcoming bottleneck in the pathway by introducing exogenous genes and optimizing gene copy numbers. By optimizing the pathway, the researchers were able to achieve high yields of nepetalactone from simple sugar in microtiter plates, paving the way for scalable production of the compound.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Cell Biology
Lukas S. Wijaya, Carina Rau, Theresa S. Braun, Serif Marangoz, Vincent Spegg, Matthijs Vlasveld, Wiebke Albrecht, Tim Brecklinghaus, Hennicke Kamp, Joost B. Beltman, Jan G. Hengstler, Bob van de Water, Marcel Leist, Stefan Schildknecht
Summary: This study found that the antibiotic NFT can transiently elevate intracellular glutathione levels by regulating the Nrf2-GCL axis, enhancing cells' resistance to various stressors.
CELL BIOLOGY AND TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Christopher S. Campomizzi, George E. Ghanatios, D. Fernando Estrada
Summary: Cytochromes P450 are versatile enzymes involved in endogenous and exogenous metabolism, undergoing structural changes related to function. This study demonstrates the utility of fluorine (19F)-NMR spectroscopy in monitoring structural changes in CYP121A1, revealing insights into its role in substrate recognition and mechanistic details of this essential enzyme from Mycobacterium tuberculosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Weixian Li, Xiaohui Ma, Guodong Li, Aili Zhang, Dong Wang, Feiyu Fan, Xiaolin Ma, Xueli Zhang, Zhubo Dai, Zigang Qian
Summary: Tunicosaponins are natural products extracted from Psammosilene tunicoides, with representative aglycones being gypsogenin and quillaic acid. Two novel cytochrome P450-dependent monooxygenases involved in the biosynthesis of tunicosaponins were identified, and the whole biosynthesis pathway of the tunicosaponin aglycones was successfully reconstituted in yeast.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mirva J. Saaranen, Heli Alanen, Kirsi E. H. Salo, Emmanuel Nji, Pekka Karkkainen, Constanze Schmotz, Lloyd W. Ruddock
Summary: Proteins in the thioredoxin superfamily, such as protein disulfide isomerase (PDI) and glutaredoxins, have similar structures and catalytic mechanisms. PDI uses glutathione for oxidation/reduction in vitro, while glutaredoxins have a high affinity for glutathione. Mutating the active site of PDI to a more glutaredoxin-like motif increases its reactivity with glutathione.
Review
Chemistry, Multidisciplinary
Iori Morita, Takahiro Mori, Ikuro Abe
Summary: Teleocidins are potent protein kinase C activators with a unique indole-fused nine-membered lactam structure synthesized through a multi-step biosynthetic process involving NRPS, cytochrome P450 oxidase, prenyltransferase, and C-methyltransferase. Recent research has focused on elucidating the molecular basis for the challenging P450-catalyzed intramolecular C-N bond formation, leading to the generation of indolactam scaffold, as well as the production of unnatural and novel molecular scaffolds through precursor-directed biosynthesis using promiscuous P450 enzymes.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Physical
Lea R. Rapp, Sergio M. Marques, Erna Zukic, Benjamin Rowlinson, Mahima Sharma, Gideon Grogan, Jiri Damborsky, Bernhard Hauer
Summary: The cytochrome P450 CYP153A(M.aq) enzyme from Marinobacter aquaeolei was engineered to hydroxylate octanoic acid with significantly improved catalytic efficiency and substrate binding. The modifications in tunnel structures and loop regions were key in stabilizing the enzyme-substrate complex and enhancing catalytic efficiency. Previous fatty acid anchor interactions were also found to boost the enzyme activity towards octanoic acid.
Article
Biochemistry & Molecular Biology
Melanie Nolden, Mark J. Paine, Ralf Nauen
Summary: Cytochrome P450 monooxygenases play a crucial role in the oxidative metabolism of xenobiotics in insects and their duplication and upregulation can lead to insecticide resistance. The interaction between P450s and other enzymes like NADPH cytochrome P450 oxidoreductase and cytochrome b5 is complex and can impact metabolic capacity. Recombinant expression of P450s in insect cells with cytochrome b5 can significantly enhance their ability to metabolize certain substrates, but not necessarily insecticides like deltamethrin.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
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
Abayomi S. Faponle, Anupom Roy, Ayodeji A. Adelegan, James W. Gauld
Summary: Cytochrome P450s (P450) are important enzymes with potential for oxy-functionalization of organic molecules, and recent research on a new member of the CYP116B family, P450-TT, suggests that it can control the entry of substrates to its active site through an elaborate substrate channel.
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
Biochemistry & Molecular Biology
Justin C. Miller, Mary A. Schuler
Summary: This study identified key residues that toggle SLS and SLAS selectivity in two CYP72A subfamily enzymes from Camptotheca acuminata. The mutations in substrate recognition sequence 1 (SRS1) determine the selectivity, and changes in other regions can also affect enzyme activity towards different substrates. Understanding the determinants of selectivity in these enzymes provides opportunities for more tailored heterologous production of TIAs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jaime D'Agostino, Haoming Zhang, Cesar Kenaan, Paul F. Hollenberg
CHEMICAL RESEARCH IN TOXICOLOGY
(2015)
Article
Biochemical Research Methods
Yoshihiro Morishima, Haoming Zhang, Miranda Lau, Yoichi Osawa
ANALYTICAL BIOCHEMISTRY
(2016)
Article
Pharmacology & Pharmacy
Hsia-lien Lin, Haoming Zhang, Paul F. Hollenberg
DRUG METABOLISM AND DISPOSITION
(2018)
Article
Biochemistry & Molecular Biology
Haoming Zhang, Adam L. Yokom, Shen Cheng, Min Su, Paul F. Hollenberg, Daniel R. Southworth, Yoichi Osawa
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Min Su, Sumita Chakraborty, Yoichi Osawa, Haoming Zhang
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Yudong Sun, Xiaoqiang Huang, Yoichi Osawa, Yuqing Eugene Chen, Haoming Zhang
Summary: This article highlights the unique features of wild-type cytochrome P450 CYP102A1 from Bacillus megaterium as a highly efficient monooxygenase, as well as the significant progress made in engineering CYP102A1 for various applications. The repertoire of engineered CYP102A1 variants continues to expand, covering a wide range of substrates. The objective of the article is to provide a concise review of the latest advancements, with reference to related literature on CYP102A1.
Article
Biochemistry & Molecular Biology
Shen Cheng, Zhiyuan Bo, Paul Hollenberg, Yoichi Osawa, Haoming Zhang
Summary: The study reports the use of amphipols to form a fully functional, soluble, homogeneous preparation of full-length CYP:POR complexes for biochemical and structural study. The stability and structure of the complex were validated using negative stain electron microscopy, revealing a tetrameric complex embedded in one amphipol nanoparticle. This represents the first report of the full-length mammalian CYP:POR complex by transmission EM and highlights the potential use of amphipols in biochemical and structural studies of functional CYP complexes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Dhiman Maitra, Eric L. Carter, Rani Richardson, Laure Rittie, Venkatesha Basrur, Haoming Zhang, Alexey Nesvizhskii, Yoichi Osawa, Matthew W. Wolf, Stephen W. Ragsdale, Nicolai Lehnert, Harald Herrmann, M. Bishr Omary
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2019)
Article
Pharmacology & Pharmacy
Dale A. Lauver, Dawn S. Kuszynski, Barbara D. Christian, Matthew P. Bernard, James P. Teuber, Bruce E. Markham, Yuqing E. Chen, Haoming Zhang
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2019)
Article
Pharmacology & Pharmacy
Hsia-lien Lin, Haoming Zhang, Vyvyca J. Walker, Jaime D'Agostino, Paul F. Hollenberg
DRUG METABOLISM AND DISPOSITION
(2017)
Article
Pharmacology & Pharmacy
Georgina C. B. Nicholl, Ali K. Jawad, Robert Weymouth, Haoming Zhang, Asim A. Beg
BRITISH JOURNAL OF PHARMACOLOGY
(2017)
Article
Pharmacology & Pharmacy
Hsia-lien Lin, Haoming Zhang, Cesar Kenaan, Paul F. Hollenberg
DRUG METABOLISM AND DISPOSITION
(2016)
Article
Pharmacology & Pharmacy
Haoming Zhang, D. Adam Lauver, Hui Wang, Duxin Sun, Paul F. Hollenberg, Y. Eugene Chen, Yoichi Osawa, Daniel T. Eitzman
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2016)
Article
Pharmacology & Pharmacy
Diane M. Calinski, Haoming Zhang, Susan Ludeman, M. Eileen Dolan, Paul F. Hollenberg
DRUG METABOLISM AND DISPOSITION
(2015)
Meeting Abstract
Chemistry, Multidisciplinary
Haoming Zhang, Paul F. Hollenberg
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2014)