Article
Multidisciplinary Sciences
Philippe Urban, Denis Pompon
Summary: Conformational dynamics is crucial for the function of multidomain electron transfer complexes. Cryo-electron microscopy provides more information on dynamics compared to crystallographic or NMR approaches. AlphaFold has successfully predicted protein complexes, but its ability to address large conformational changes involved in catalysis has been unclear. In this study, a competitive modelling approach (CMA) was used to assess alternate conformations of the bacterial CYP102A1 monooxygenase homodimer. The predictions were compared to crystallographic and cryo-EM data, showing consistencies and allowing reinterpretation of experimental data.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Michael J. Martinez, Jessica D. Carder, Evan L. Taylor, Eric P. Jacobo, ChulHee Kang, J. A. Brozik
Summary: This study measured the thermodynamic driving forces responsible for how strongly CPR partitions into a biomimetic ER with the same lipid composition. Results showed that the redox states of CPR have a significant impact on these driving forces.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biology
Jiannan Li, Noriyuki Hamaoka, Fumiaki Makino, Akihiro Kawamoto, Yuxi Lin, Matthias Roegner, Marc M. Nowaczyk, Young-Ho Lee, Keiichi Namba, Christoph Gerle, Genji Kurisu
Summary: By studying the high-resolution structure of the cyanobacterial photosystem I complexed with Ferredoxin, we have explained the details of its electron transfer process and proposed a possible mechanism for electron transfer. This helps us to better understand the function of Photosystem I.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Grant Eilers, Kushol D. Gupta, Audrey Allen, Saira E. Montermoso, Hemma J. Murali, Robert E. Sharp, Young J. Hwang, Frederic D. E. Bushman, Gregory J. Van Duyne
Summary: HIV integrase plays a crucial role in viral replication by inserting viral DNA into the host genome. Strand transfer inhibitors (STIs) and allosteric inhibitors of integrase (ALLINIs) are two major classes of antivirals that target integrase. In this study, we determined the crystal structure of the minimal ternary complex between the catalytic core domain (CCD), carboxy-terminal domain (CTD), and the ALLINI BI-224436, providing insights for improving ALLINI design and minimizing resistance.
Article
Biochemistry & Molecular Biology
Narayanan Srividya, Iris Lange, Jana K. Richter, Matthias Wuest, B. Markus Lange
Summary: In this study, the enantioselectivity of multiple enzymes involved in monoterpenoid biosynthesis in peppermint and Japanese catnip was investigated. The experimental results showed that these enzymes exhibited different enantioselectivity towards intermediates of the pathway, and molecular modeling studies supported the experimental data. This study lays the groundwork for further structure-function studies on the origin of enantioselectivity in closely related species of the Lamiaceae.
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
Biochemistry & Molecular Biology
Nataliia Kovalchuk, Joseph L. Jilek, Laura S. Van Winkle, Nathan J. Cherrington, Xinxin Ding
Summary: The study used a lung-Cpr-null mouse model to investigate the role of lung POR in PQ-induced pulmonary fibrosis, finding that CPR plays a critical role in this process.
Article
Ecology
Xiaoman Zhang, Zhiyong Shi, Cai-qing Yang, Jing Li, Jingze Liu, Ai-bing Zhang
Summary: This study identified a co-orthologous gene, CYP4g15, in insects that originated from different bacteria species, suggesting its functional conservation and ancient origin.
FRONTIERS IN ECOLOGY AND EVOLUTION
(2022)
Article
Pharmacology & Pharmacy
Melina Lopez, Pedro F. Malacarne, Anna Gajos-Draus, Xinxin Ding, Andreas Daiber, Jon O. Lundberg, Stefan Offermanns, Ralf P. Brandes, Flavia Rezende
Summary: The study suggests that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates, while ALDH2 plays an important role in activating organic nitrates.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Justin C. Miller, Allison J. Hollatz, Mary A. Schuler
Summary: The study identifies differences in the terpene indole alkaloid (TIA) pathways in Catharanthus roseus and Camptotheca acuminata, and demonstrates the ability of specific P450 proteins to convert certain compounds in these pathways. The research provides valuable tools for further examination of substrate recognition and the unique mechanism of C-C bond scission involved in these pathways.
Article
Chemistry, Medicinal
Soudeh Bahramian Nasab, Ahmad Homaei, Roberto Fernandez-Lafuente, Jon Del Arco, Jesus Fernandez-Lucas
Summary: The use of marine enzymes as catalysts for biotechnological applications is a hot topic. In this study, a liver NADPH-dependent cytochrome P450 reductase (CPR) from the marine fish Liza klunzingeri (LkCPR) was isolated, purified and biochemically characterized. LkCPR showed remarkable catalytic features, such as a wide range of pH and temperature stability, high catalytic activity, and highest thermostability among reported CPRs. These findings suggest that LkCPR has great potential as a biocatalyst.
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
Biochemistry & Molecular Biology
Tianyi Yu, Marzhana Omarova, Meng Zhang, Istiak Hossain, Jianqiang Chen, Omead Darvish, Vijay T. John, Donghui Zhang
Summary: The cellular functions of membrane proteins are closely related to their structures and aggregation states. We have investigated the fragmentation of synthetic liposomes using hydrophobe-containing polypeptoids (HCPs). Our findings demonstrate that HCPs can effectively induce the fragmentation of liposomes into colloidally stable nanoscale HCP-lipid complexes, and have the potential for novel macromolecular surfactants for membrane protein extraction.
Article
Biotechnology & Applied Microbiology
Ru-Yi Ye, Juan Song, Zhi-Jun Zhang, Hui-Lei Yu
Summary: CYP120As are unique non-membrane P450 enzymes that play a significant role in the biodegradation of retinoids, with promising catalytic potential.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
