Review
Biochemistry & Molecular Biology
Giulia Calloni, R. Martin Vabulas
Summary: Understanding the role of FAD in mammalian cryptochromes is crucial for comprehending circadian rhythms in human health and disease. While the weak binding of FAD in vitro suggests it may be functionless, the FAD-binding pocket is important for ubiquitylation and stabilization of cryptochromes. Studies have shown that increased supplies of FAD stabilize cryptochromes in cell culture and depletion of the FAD precursor affects the expression of circadian genes in mice.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Richard Niese, Ketaki Deshpande, Michael Mueller
Summary: A ferredoxin from Archaeoglobus fulgidus has been identified that regenerates the cofactor in the corresponding geranylgeranyl reductase (GGR) for the reduction of isolated C=C bonds. The reaction was coupled to an unspecific ferredoxin reductase from E. coli and a glucose dehydrogenase/glucose regeneration system for NAD(P)+ to enable reactions with purified enzymes. Moreover, reactions can be performed in E. coli cell-free extracts.
Article
Biotechnology & Applied Microbiology
Xiaowang Zhang, Zhuotao Tan, Chaojian Li, Siyu Qi, Mengjiao Xu, Ming Li, Wenlong Xiong, Wei Zhuang, Dong Liu, Chenjie Zhu, Hanjie Ying
Summary: This study established a novel system combining horse liver alcohol dehydrogenase (HLADH) with synthetic bridged flavin cofactor for efficient synthesis of lactones, including chiral lactones, from diols. The system showed better regeneration efficiency and product yield compared to previous NAD(P)(+) regeneration systems. A two-phase system was further applied to achieve 80% yield at 300 mM substrate.
BIORESOURCES AND BIOPROCESSING
(2021)
Article
Biochemistry & Molecular Biology
Elena Maklashina, Tina M. Iverson, Gary Cecchini
Summary: The membrane-bound complex II family of proteins consists of enzymes that catalyze conversions between succinate and fumarate while oxidizing or reducing qui-nones within the membrane domain. These enzymes are primarily protein heterotetramers with various subunits containing different redox centers.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
John S. Samuelian, Thomas J. Gremminger, Zhenwei Song, Raghav R. Poudyal, Jun Li, Yuanzhe Zhou, Seth A. Staller, Johan A. Carballo, Manami Roychowdhury-Saha, Shi-Jie Chen, Donald H. Burke, Xiao Heng, Dana A. Baum
Summary: The discovery of an RNA aptamer that preferentially binds oxidized forms of flavin and alters flavin's reduction potential suggests that differential affinity could have played a crucial role in the metabolism of primordial RNAs in an RNA world.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sunghark Kwon
Summary: This study analyzed the structure of FADS from the human pathogen Streptococcus pneumoniae and predicted possible substrate-binding modes, providing a structural basis for understanding the catalytic mechanism of SpFADS and developing novel inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Archana Iyer, Renata A. G. Reis, Johnson Agniswamy, Irene T. Weber, Giovanni Gadda
Summary: The crystal structure of D-arginine dehydrogenase from Pseudomonas aeruginosa has been determined, revealing the versatility of the reduced flavin in performing multiple functions at the same active site.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Crystallography
Stephanie Luedtke, Celine Bojo, Yunshen Li, Emilio Luna, Bianca Pomar, Zoran Radic
Summary: The structures of OP-inhibited human acetylcholinesterases have shown similar backbone conformations except for the diethylphosphoryl-hAChE conjugate, where large ethoxy group insertion led to notable loop distortions. Despite the snug fit of large substituents on phosphorus, only minor conformational changes were detected in Novichok-conjugated hAChEs due to the movement of the entire OP away from the acyl pocket. The observation that AChE's small acyl pocket can accommodate larger substituents if the OP is pulled away has practical implications for structure-based design and specificity definition.
Article
Crystallography
Zoran Radic
Summary: The study analyzed the influence of ligand binding on the backbone structures of human, mouse, and Torpedo californica acetylcholinesterase, revealing that the acyl pocket loop is the most conformationally adaptive element. Ligand binding can trigger potential allosteric interactions within the AChE backbone, while the aromatic choline binding site has a stabilizing effect by attracting and pulling fitting entities covalently tethered to the active Ser, facilitating catalytic reactions or relieving steric pressure. These dynamic properties inferred from static X-ray structures contribute to a better understanding of the molecular template important for designing therapeutically active molecules like AChE inhibitors and reactivators of conjugated, inactive AChE.
Article
Biochemistry & Molecular Biology
Andrea Moreno, Victor Taleb, Maria Sebastian, Ernesto Anoz-Carbonell, Marta Martinez-Julvez, Milagros Medina
Summary: The biosynthesis of flavins involves two enzymes, RFK and FMNAT, with different structural and functional characteristics in bacteria and mammals. Prokaryotic FADS, including those from pathogens, show variability in less conserved regions, allowing for alternative strategies in flavin homeostasis. Targeting FADSs from pathogens could lead to species-specific inhibitors.
Article
Biochemistry & Molecular Biology
Panu Pimviriyakul, Pimchai Chaiyen
Summary: This study investigates the key features stabilizing C4a-adducts in HadA by using transient kinetics, site-directed mutagenesis, and pH-dependent behaviors. It identifies Arg101 and Asn447 as key residues that play important roles in FADH(-) binding and C4a-hydroperoxy-FAD formation in HadA. Additionally, the formation of C4a-hydroxy-FAD is pH insensitive, while its dehydration to oxidized FAD is associated with pH.
Article
Biotechnology & Applied Microbiology
Ying Hou, Wanying Zhao, Xincheng Ding, Xuan Zhang, Zhibin Li, Zhilei Tan, Jingwen Zhou, Hongxing Wang, Shiru Jia
Summary: Efficient FAD/FADH(2) regeneration was achieved through a combination of l-amino acid deaminase (l-AAD) and halogenase (CombiAADHa). The system successfully catalyzed the conversion of l-amino acid to halide and α-keto acid, yielding 170 mg/L of 7-chloro-tryptophan (7-Cl-Trp) and 193 mg/L of indole pyruvic acid (IPA) within 6 hours. The use of ultrasound treatment further improved the yields by 1.6- and 1.4-fold for 7-Cl-Trp and IPA, respectively.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nishya Mohamed-Raseek, Anne-Frances Miller
Summary: This study investigated the importance of Arg residues in bifurcating electron transfer flavoproteins (Bf ETFs), and found that removal of positive charge in the electron transfer (ET) site reduces the single electron carrier property of the ET flavin, while removal of positive charge in the bifurcating (Bf) site affects protein stability. They proposed a mechanism of interaction between Arg residues and FAD or AMP, and provided a model to explain their roles.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tyler B. Alt, Matthew R. Hoag, Graham R. Moran
Summary: This article presents the first comprehensive kinetic investigation of a bacterial form of DPD, revealing its similarity to the mammalian form in terms of mechanism but with distinct aspects in substrate roles.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Michele Partipilo, Guang Yang, Maria Laura Mascotti, Hein J. Wijma, Dirk Jan Slotboom, Marco W. Fraaije
Summary: This study investigates the biochemical characteristics of SthA and reveals its oxidase activity, producing hydrogen peroxide and superoxide anion. The importance of the evolutionarily conserved sequence motif in SthA function is also highlighted.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)