Article
Biochemistry & Molecular Biology
Itsumi Tani, Shogo Ito, Yukiko Shirahata, Yutaka Matsuyama, James G. Omichinski, Yasuyuki Shimohigashi, Rui Kamada, Kazuyasu Sakaguchi
Summary: The study investigated the roles of two Arg residues in the metal-dependent protein phosphatase PPM1A on dephosphorylation activity. Results indicated that both Arg residues were crucial for enzymatic activity, with Arg186 positioned to interact with the substrate phosphate group. The significance of each Arg residue in catalysis depended on the specific substrate.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Plant Sciences
Hui Xu, Zhen Li, Peng-Fei Jiang, Li Zhao, Chang Qu, Yves Van de Peer, Yan-Jing Liu, Qing-Yin Zeng
Summary: Enzymes are essential for all living systems, and in plants, the glutaredoxin (GRX) family of enzymes plays important roles in development and stress tolerance. This study identified and classified 41 GRX genes in the poplar genome based on differences in gene structure, expression patterns, subcellular localization, enzymatic activity, and substrate specificity. Site-directed mutagenesis revealed that the divergence of active site motifs among different classes of GRX proteins led to substrate switches, providing new insights into the molecular evolution of these important plant enzymes.
Review
Biochemistry & Molecular Biology
Hieu Nguyen, Arminja N. Kettenbach
Summary: Dynamic protein phosphorylation and dephosphorylation play critical roles in cellular signaling and biological functions. Dysregulation of these processes has been linked to various human diseases. This review focuses on the mechanisms controlling the specific dephosphorylation of proteins. The majority of serine/threonine dephosphorylation is catalyzed by highly conserved phosphoprotein phosphatase (PPP) catalytic subunits, which form holoenzymes with regulatory and scaffolding subunits. PPP holoenzymes recognize phosphorylation site consensus motifs and interact with short linear motifs (SLiMs) or structural elements distal to the phosphorylation site. Recent advances in understanding the mechanisms of PPP site-specific dephosphorylation preference and substrate recruitment are discussed, with emphasis on their roles in regulating cell division.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nathan L. Ponzar, Razia Tajwar, Nicola Pozzi, John E. Tavis
Summary: This study investigated the mechanism of action of alpha-hydroxytropolones (alpha HTs) as anti-RNase H inhibitors against human RNase H1 enzyme. The researchers found that alpha HTs stabilize an inactive enzyme-substrate-inhibitor complex, reducing the enzyme's activity. This discovery will aid in the development of selective RNase H inhibitors for viral enzymes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Can Ozden, Roman Sloutsky, Tomohiro Mitsugi, Nicholas Santos, Emily Agnello, Christl Gaubitz, Joshua Foster, Emily Lapinskas, Edward A. Esposito, Takeo Saneyoshi, Brian A. Kelch, Scott C. Garman, Yasunori Hayashi, Margaret M. Stratton
Summary: This study investigates the activation mechanism of CaMKII using X-ray crystallography, molecular dynamics simulations, and biochemistry. The results show that contrary to the previously believed two distinct sites, activators and substrates actually bind to a single continuous site on the kinase domain. Through kinetic competition with the regulatory segment, high-affinity binding partners sustain the activity of CaMKII, allowing substrate phosphorylation.
Article
Biochemistry & Molecular Biology
Charline Mary, Mona Hoseini Soflaee, Rushendhiran Kesavan, Muriel Gelin, Harrison Brown, G. Zacharias, Thomas P. Mathews, Andrew Lemoff, Corinne Lionne, Gilles Labesse, Gerta Hoxhaj
Summary: NAD+ kinases (NADKs) are metabolite kinases that phosphorylate NAD+ molecules to generate NADPH. The crystal structure of human NADK2 reveals a substrate-driven mode of activation and unexpected dimeric organization. Acetylation events on NADK2 inhibit its activity and reduce mitochondrial NADPH and proline metabolism.
Article
Biochemistry & Molecular Biology
Gui-Xin Peng, Yong Zhang, Qin-Qin Wang, Qing-Run Li, Hong Xu, En-Duo Wang, Xiao-Long Zhou
Summary: The study revealed the crucial role of GTPBP3 in tRNA modification and its pathogenic mutations affecting structure, function, or localization. Additionally, a novel cytoplasm-localized isoform of hGTPBP3 was identified, suggesting potential noncanonical functions.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Ryan P. Sweeney, Phillip M. Danby, Andreas Geissner, Ryan Karimi, Jesper Brask, Stephen G. Withers
Summary: Efforts have been made to find better amylase mutants through high-throughput screening, aided by the development of efficient active site titration reagents for quantitation of active mutants in crude cell lysates. The designed reagent incorporates a highly reactive fluorogenic leaving group onto unsaturated cyclitol ethers, providing a convenient titrant for alpha-amylases down to low nanomolar levels.
Article
Chemistry, Multidisciplinary
Robbins Puthenveetil, Shelby A. Auger, Natalia Gomez-Navarro, Mitra Shumsher Rana, Riki Das, Liam Brendan Healy, Kiall F. Suazo, Zhen-Dan Shi, Rolf E. Swenson, Mark D. Distefano, Anirban Banerjee
Summary: Protein palmitoylation is the most prevalent form of protein lipidation and is involved in various cellular processes and human diseases. There is currently no global strategy to identify physiological substrates of individual zDHHC enzymes. This study outlines a general approach using synthetic orthogonal substrates to accomplish this task.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Neil J. Rzechorzek, Simone Kunzelmann, Andrew G. Purkiss, Mariana Silva Dos Santos, James I. MacRae, Ian A. Taylor, Kasper Fugger, Stephen C. West
Summary: This study presents the crystal structures and catalytic process of DNPH1, providing important insights for inhibitor design. Inactivation of DNPH1 increases the incorporation of hmdU into DNA, making BRCA-deficient cells more sensitive to PARP inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maria-Soledad Orellana, Gonzalo A. Jana, Maximiliano Figueroa, Jose Martinez-Oyanedel, Fabiola E. Medina, Estefania Tarifeno-Saldivia, Marcell Gatica, Maria Angeles Garcia-Robles, Nelson Carvajal, Elena Uribe
Summary: Arginase and agmatinase have similarities, but show different specificities for their substrates, with loop A and loop B playing crucial roles in the specificity of arginase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Cedric Gastaldi, Rolande Ngahan Tagne, Victor Laurent, Virgil Helaine, Jean-Louis Petit, Mounir Traikia, Veronique de Berardinis, Marielle Lemaire, Christine Guerard-Helaine
Summary: Originally named for their specific nucleophile specificity towards pyruvate, some pyruvate aldolases were shown to convert other nucleophiles, successfully reacting with various aldehydes and even ketones. Unknown aldols with a 3S configuration were isolated and characterized, with their stereochemistries determined as either 4R or 4S by selecting the appropriate aldolase.
Review
Engineering, Chemical
Yuko Tsuda, Koushi Hidaka, Keiko Hojo, Yoshio Okada
Summary: Plasmin, a serine protease responsible for fibrinolysis pathway and pathology events, has inhibitors designed to bind to its active site, preventing it from digesting substrates. These inhibitors have potential as anti-inflammatory and anti-cancer agents, with second-generation inhibitors optimized for both activity and selectivity. This review focuses on the relationship between Plasmin inhibitors' inhibitory activity and structure for design and clinical application purposes.
Review
Chemistry, Medicinal
Zheng Zhao, Philip E. Bourne
Summary: This article reviews the recent developments in covalent kinase inhibitors (CKIs) and discusses their characteristics, including the features of nucleophilic amino acids and preferences of electrophilic warheads. It also explores trends in CKI development across the whole proteome.
Article
Biochemistry & Molecular Biology
Carolina Conter, Filippo Favretto, Paola Dominici, Luis Alfonso Martinez-Cruz, Alessandra Astegno
Summary: This study explored the role of hydroxyl moieties of S84, Y160, and Y246 residues in determining the L-serine/L-OAS preference in TgCBS. It was found that the triple mutant S84A/Y160F/Y246V behaved like an OCBS, showing beta-replacement activity only with L-OAS. The hydroxyl group of Y246 plays a major role in controlling L-serine preference by efficiently stabilizing its leaving group. These findings provide a better understanding of substrate specificity in TgCBS and have implications for the design of new antimicrobial compounds.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Chemistry, Medicinal
Pravin Muthu, Stefan Lutz
Article
Biochemistry & Molecular Biology
Stephan Reitinger, Ying Yu, Jacqueline Wicki, Martin Ludwiczek, Igor D'Angelo, Simon Baturin, Mark Okon, Natalie C. J. Strynadka, Stefan Lutz, Stephen G. Withers, Lawrence P. McIntosh
Article
Biochemistry & Molecular Biology
Ashley B. Daugherty, Pravin Muthu, Stefan Lutz
Article
Chemistry, Medicinal
Yongfeng Li, Priti B. Soni, Lingfeng Liu, Xiao Zhang, Dennis C. Liotta, Stefan Lutz
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Editorial Material
Biochemistry & Molecular Biology
Romas Kazlauskas, Stefan Lutz
CURRENT OPINION IN CHEMICAL BIOLOGY
(2009)
Article
Biochemistry & Molecular Biology
Joseph A. Laszlo, Ying Yu, Stefan Lutz, David L. Compton
JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC
(2011)
Article
Biochemical Research Methods
Elsie M. Williams, Se Min Jung, Jennifer L. Coffman, Stefan Lutz
ACS SYNTHETIC BIOLOGY
(2018)
Article
Biochemical Research Methods
Matthew C. Jenkins, Stefan Lutz
Summary: The study demonstrates the successful concurrent surface functionalization and internal packaging of encapsulins from Thermotoga maritima to create a catalytically competent two-enzyme metabolon, highlighting the engineerability of encapsulins as flexible scaffolds for biocatalytic applications. These engineered encapsulins functioned at speeds equivalent to those of the two enzymes freely dispersed in solution, emphasizing their potential in biotechnology and synthetic biology.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Monica L. Gerth, Stefan Lutz
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2007)
Article
Chemistry, Multidisciplinary
Z Qian, S Lutz
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2005)
Article
Biochemistry & Molecular Biology
PTR Rajagopalan, S Lutz, SJ Benkovic