Article
Biochemistry & Molecular Biology
Christoph P. Sager, Susanne Weber, Matthias Negri, Pauline Banachowicz, Gabriele Moeller, Jerzy Adamski, Rolf W. Hartmann, Sandrine Marchais-Oberwinkler
Summary: This study aimed to determine the topology of 17 beta-Hydroxystemid dehydrogenase type 2 (17β-HSD2) by constructing a homology model in complex with NAD(+) and 17 beta-estradiol, which was confirmed to be of high quality through site-directed mutagenesis. The model identified key amino acids involved in ligand or internal structure stabilization, providing a basis for further experiments and drug design studies.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Microbiology
Zhizeng Sun, Timothy Palzkill
Summary: The study identified essential active-site residues of the MCR-1 enzyme using deep sequencing, which are critical for its polymyxin resistance function. Approximately 75% of the residues examined were found to be essential for the enzyme's function, suggesting inhibitors binding near these sites will broadly inhibit MCR-1 and similar enzymes.
Review
Chemistry, Organic
Houchao Xu, Jeroen S. Dickschat
Summary: In the past three decades, numerous terpene synthases have been characterized from various life kingdoms. The mechanisms of terpene synthases have been investigated through site-directed mutagenesis, providing valuable insights into their catalysis and resulting in mutants with improved yields.
SYNTHESIS-STUTTGART
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Matsui, Norifumi Muraki, Ke Chen, Tomoya Mori, Aaron A. Ingram, Keiko Oike, Harald Groger, Shigetoshi Aono, Yasuhisa Asano
Summary: Aldoxime dehydratase (Oxd) is a heme enzyme that catalyzes aldoxime dehydration to nitriles. This study reports the crystal structure of OxdB from Bacillus sp. OxB-1 and the factors influencing substrate specificity.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Dali, Thomas Gabler, Federico Sebastiani, Alina Destinger, Paul Georg Furtmueller, Vera Pfanzagl, Maurizio Becucci, Giulietta Smulevich, Stefan Hofbauer
Summary: Coproporphyrin ferrochelatases (CpfCs) are enzymes that catalyze the penultimate step in the coproporphyrin-dependent heme biosynthesis pathway. The discovery of the correct substrate for these ferrochelatases and the characterization of their binding mode provide valuable insights into the iron insertion process. This knowledge is essential for understanding the preconditions and mechanisms of iron insertion in CpfCs.
Article
Biochemistry & Molecular Biology
Victoria J. Laye, Shiladitya DasSarma
Summary: In this study, mutations were introduced into an Antarctic haloarchaeon enzyme to investigate its temperature-dependent catalytic activity. The results suggest that a small number of residues, located distant from the active site, mediate complex and subtle effects on the enzyme's kinetic properties at different temperatures.
Article
Chemistry, Multidisciplinary
Christian A. Gomez, Dibyendu Mondal, Qian Du, Natalie Chan, Jared C. Lewis
Summary: Directed evolution was used to engineer variants of SadX, resulting in site-selective azidation and succinylation of amino acids and amines. This study provides a promising starting point for evolving SadX variants that can functionalize structurally distinct substrates and enable enzymatic C-H functionalization with non-native functional groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
News Item
Biochemistry & Molecular Biology
Emil Martin
Summary: The susceptibility of nitric oxide to scavenging and oxidation restricts its availability and signaling role. However, recent studies suggest that a NO-ferroheme adduct is resistant to these limitations and may function as an alternative signaling molecule derived from nitric oxide in vasculature.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Haoran Yu, Shuang Ma, Yiwen Li, Paul A. Dalby
Summary: Directed evolution is a powerful strategy to engineer protein properties, and hot spot prediction is crucial for producing smart libraries. Selection of hot spots based on sequence and structure allows for efficient generation of proteins with desired properties.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Chemistry, Physical
Matthew N. Podgorski, Joshua S. Harbort, Joel H. Z. Lee, Giang T. H. Nguyen, John B. Bruning, William A. Donald, Paul Bernhardt, Jeffrey R. Harmer, Stephen G. Bell
Summary: In this study, it was found that mutating a highly conserved threonine residue in CYP199A4 to glutamate can convert it to a peroxygenase and improve its peroxygenase activity. The crystal structure of the mutant demonstrated a change in spin state upon substrate binding, which was linked to the modification of the oxygen-binding groove and the retention of the iron-bound aqua ligand. The detailed characterization of this engineered heme peroxygenase will aid in the development of new methods for the selective C-H bond activation using heme enzymes.
Article
Biotechnology & Applied Microbiology
Tingting Wang, Zhiming Jiang, Yiya Wang, Hao Wu, Yan Fang, Weiliang Dong, Bin Wu, Jiangfeng Ma, Min Jiang
Summary: Mutation of amino acids near the sucrose binding site of dextransucrase can affect the chain elongation process, making it possible to modulate dextran size.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Physical
Meng Huang, Salila Pengthaisong, Ratana Charoenwattanasatien, Natechanok Thinkumrob, Jitrayut Jitonnom, James R. Ketudat Cairns
Summary: This study investigated the importance of glucose-binding residues in GH116 beta-glucosidases through mutagenesis, kinetic characterization, X-ray crystallography, and ONIOM calculations. The mutations significantly affected the enzyme's catalytic properties, and the amino acid residues involved in glucose binding showed strong electrostatic interactions with the substrate. These findings have important implications for the design of inhibitors and the improvement of GH116 enzymes for various applications.
Article
Biochemistry & Molecular Biology
Matthew N. Podgorski, Joel H. Z. Lee, Joshua S. Harbort, Giang T. H. Nguyen, Daniel Z. Doherty, William A. Donald, Jeffrey R. Harmer, John B. Bruning, Stephen G. Bell
Summary: Cytochrome P450 enzymes (CYPs) are heme-thiolate monooxygenases that catalyze the insertion of an oxygen atom into the C-H bonds of organic molecules. In this study, a mutation of the threonine residue of the acid-alcohol pair in CYP199A4 was found to induce peroxygenase activity. The mutation resulted in a strengthened interaction between the glutamate side chain and the distal aqua ligand of the heme, preventing its displacement by ligands. This explains why the mutant enzyme can switch to peroxygenase activity and shut down the monooxygenase pathway.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Review
Chemistry, Inorganic & Nuclear
Sam P. de Visser, Yen-Ting Lin, Hafiz Saqib Ali, Umesh Kumar Bagha, Gourab Mukherjee, Chivukula Sastri
Summary: This paper discusses the research progress on product selectivity in bioinorganic chemistry, focusing on the dominant role and mechanism of negative catalysis in enzymatic reactions.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Amanda Lyn Robinson, Jean-Noel Rebilly, Regis Guillot, Christian Herrero, Helene Maisonneuve, Frederic Banse
Summary: We report two new Fe-III complexes obtained by replacing pyridines by phenolates in a known non-heme aminopyridine iron complex. These complexes demonstrate good O-2 activation ability and can serve as important activators in electrochemical setups to achieve substrate oxidation.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Crystal R. Archer, Benjamin T. Enslow, Alexander B. Taylor, Victor De la Rosa, Akash Bhattacharya, Mark S. Shapiro
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Cell Biology
Sowmya Balasubramanian, Lavanya Pandranki, Suzanna Maupin, Kumaraguruparan Ramasamy, Alexander B. Taylor, Peter John Hart, Joel B. Baseman, Thirumalai R. Kannan
CELLULAR MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Laura Jo Sherwood, Alexander Bryan Taylor, Peter John Hart, Andrew Hayhurst
JOURNAL OF MOLECULAR BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Meghan Guzman, Anastasia Rugel, Reid S. Tarpley, Xiaohang Cao, Stanton F. McHardy, Philip T. LoVerde, Alexander B. Taylor
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2020)
Article
Parasitology
Anastasia R. Rugel, Meghan A. Guzman, Alexander B. Taylor, Frederic D. Chevalier, Reid S. Tarpley, Stanton F. McHardy, Xiaohang Cao, Stephen P. Holloway, Timothy J. C. Anderson, P. John Hart, Philip T. LoVerde
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2020)
Article
Infectious Diseases
Meghan A. Guzman, Anastasia R. Rugel, Reid S. Tarpley, Sevan N. Alwan, Frederic D. Chevalier, Dmytro P. Kovalskyy, Xiaohang Cao, Stephen P. Holloway, Timothy J. C. Anderson, Alexander B. Taylor, Stanton F. McHardy, Philip T. LoVerde
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Biochemistry & Molecular Biology
Kevin W. Sea, Alexander B. Taylor, Susan T. Thomas, Amir Liba, Isabelle B. Bergman, Stephen P. Holloway, Xiaohang Cao, Edith B. Gralla, Joan S. Valentine, P. John Hart, Ahmad Galaleldeen
Summary: The study characterizes the biophysical properties of a plant SOD1 from tomato chloroplasts and presents a unique crystal structure where zinc is found in the copper-binding site but not in the zinc-binding site. This alternate conformation of D83 appears to be responsible for the previously observed pH-dependent loss of zinc from the zinc-binding site of SOD1.
Article
Biochemistry & Molecular Biology
Christopher P. Martin, Manyun Chen, Maria F. Martinez, Yousong Ding, Jonathan D. Caranto
Summary: TxtE is involved in NO-dependent Trp nitration, and the resistance of the intermediate to reduction is a key feature, allowing efficient nitration activity.
Article
Parasitology
Philip T. LoVerde, Sevan N. Alwan, Alexander B. Taylor, Jayce Rhodes, Frederic Chevalier, Timothy JC. Anderson, Stanton F. McHardy
Summary: Human schistosomiasis is a debilitating disease affecting millions globally, with drug resistance being a major concern. Scientists have identified novel drug derivatives effective against all species of the parasite, aiming to combat resistance and improve treatment outcomes.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Biochemistry & Molecular Biology
Zhongxin Ma, Ashley A. Holland, Ilana Szlamkowicz, Vasileios Anagnostopoulos, Maria Luiza Caldas D. Nogueira, Jonathan D. L. Caranto, Victor Davidson
Summary: The hemerythrin-like protein from Mycobacterium kansasii (Mka HLP) is a unique oxo-bridged diiron protein found only in mycobacterial species that cause respiratory disorders in humans. The study reveals that Mka HLP exhibits catalase activity and undergoes changes in absorbance when exposed to nitric oxide (NO). It is shown that Mka HLP can convert NO to nitrite (NO2-) and nitrate (NO3-), and also exhibits NO peroxidase activity. These findings highlight the important role of Mka HLP in deterring nitrosative stress and adapting to hypoxic conditions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Kara A. Strickland, Ashley A. Holland, Alan Trudeau, Ilana Szlamkowicz, Melanie J. Beazley, Vasileios A. Anagnostopoulos, David E. Graham, Jonathan D. Caranto
Summary: The study demonstrates that NnlA does not require nonheme iron but needs heme cofactor reduction to activate the degradation of NNG. NnlA is a homodimeric heme-binding PAS domain protein.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Meghan A. Guzman, Anastasia Rugel, Sevan N. Alwan, Reid Tarpley, Alexander B. Taylor, Frederic D. Chevalier, George R. Wendt, James J. Collins, Timothy J. C. Anderson, Stanton F. McHardy, Philip T. LoVerde
Summary: Oxamniquine has been reengineered to be effective against multiple Schistosoma species. The mode of action of its derivatives is confirmed to be conserved, and the expression of sulfotransferase in different species has been analyzed. The ability of multiple cells to express sulfotransferase is hypothesized to contribute to the effectiveness of the derivatives in killing adult worms.
Article
Chemistry, Inorganic & Nuclear
Wesley J. Transue, Rae Ana Snyder, Jonathan D. Caranto, Donald M. Kurtz Jr, Edward I. Solomon
Summary: This paper describes a particle swarm optimization (PSO) algorithm for fitting ground-state spin Hamiltonian parameters from variable-temperature/variable-field magnetic circular dichroism (MCD) data. The PSO algorithm is used to determine the ground state of two catalytic intermediates from a flavodiiron protein with nitric oxide reductase activity. The fits of the spin Hamiltonians provide important geometric and electronic insight into these species.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nathaniel E. Clark, Adam Katolik, Anastasia Welch, Christoph Schorl, Stephen P. Holloway, Jonathan P. Schuermann, P. John Hart, Alexander B. Taylor, Masad J. Damha, William G. Fairbrother
Summary: The study shows that the RNA lariat debranching enzyme Dbr1 is capable of hydrolyzing branched RNAs containing a phosphorothioate linkage at a much slower rate than native phosphate linkages. The crystal structure of the enzyme in a product-bound state provides atomic details that can aid the design of inhibitors. Dbr1 inhibitors could have therapeutic potential for major diseases such as HIV, ALS, cancer, and viral encephalitis.
Article
Multidisciplinary Sciences
Yashpal Rawal, Lijia Jia, Aviv Meir, Shuo Zhou, Hardeep Kaur, Eliza A. Ruben, Youngho Kwon, Kara A. Bernstein, Maria Jasin, Alexander B. Taylor, Sandeep Burma, Robert Hromas, Alexander V. Mazin, Weixing Zhao, Daohong Zhou, Elizabeth V. Wasmuth, Eric C. Greene, Patrick Sung, Shaun K. Olsen
Summary: This study reports cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal the participation of the amino-terminal domains of RAD51B, RAD51C and RAD51D in inter-subunit interactions for complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis provides insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Additionally, the cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer inactivate DNA binding and the HR mediator activity of BCDX2.