Editorial Cite This: Biochemistry 2018, 57, 3085−3086
pubs.acs.org/biochemistry
Special Issue: Current Topics in Mechanistic Enzymology tarting with its first issue in 1962, enzymology has been an integral focus of Biochemistry. With the leadership of its first three Editors, Hans Neurath, Gordon G. Hammes, and Richard N. Armstrong, Biochemistry has been the leading journal for publication of landmark articles in mechanistic enzymology. In the following 56 years and as new techniques have been developed, e.g., cloning, site-directed mutagenesis, and genome sequencing as well as advances in X-ray crystallography, computation, and spectroscopy, mechanistic enzymology as well as the entire field of “biochemistry” have become increasingly sophisticated in the questions that can be asked and the impact of those questions not only on protein structure and enzyme mechanism but also on biology. Now, with the leadership of Alanna Schepartz, the current Editor-in-Chief, Biochemistry is publishing articles in chemical biology, neurochemistry, and immunochemistry to keep pace with the evolution of the field of biochemistry. As Biochemistry undergoes this expansion in scope, it is important for the readership to realize that the journal still recognizes the importance of mechanistic enzymology. This special issue, “Current Topics in Mechanistic Enzymology,” includes Perspectives, Communications, and Articles that confirm that Biochemistry is maintaining its leadership role. I would like to thank Karen Allen (Boston University), Squire Booker (Pennsylvania State University), Tobias Erb (Max Planck Institute for Terrestrial Microbiology), Tom Meek (Texas A&M University), Andrew Murkin (University of Buffalo), and Satish Nair (University of Illinois, Urbana− Champaign) for their help in organizing this special issue. As summarized in the next sections, the articles in this special issue range from “basics,” such as hydrogen bonding and kinetics, to “new advances,” such as the mechanisms of novel enzymes in natural products biosynthesis. Please explore these articles and enjoy the best of mechanistic enzymology!
S
product and stereochemical outcome of terpene cyclization. A Perspective from Hening Lin (Cornell) summarizes diphthamide biosynthesis, focusing in particular on the mechanism of radical SAM enzyme Dph2. Amy Rosenzweig (Northwestern) describes sequence and activity analysis of methanobactins, copper-chelating natural products produced in bacteria. Manajit Hayer-Hartl (Max Planck Institute of Biochemistry) reviews the progress made in engineering the plant enzyme ribulose-1,5bisphosphate carboxylase/oxygenase (Rubisco) for industrial and agricultural purposes, with a focus on the molecular chaperones that aid in its assembly. A mini-review from Changming Zhao and Pinghua Liu (Boston University) summarizes the biosynthesis of sulfur-containing molecules with a particular focus on the recent progress in ergothioneine biosynthesis. Recent developments in the biosynthesis of cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) are reviewed by Satish Nair (University of Illinois, Urbana−Champaign). Craig Townsend (Johns Hopkins) describes a mechanistic study of β-lactam formation by a nonribosomal peptide synthetase. Xinqiang Xie and David Cane (Brown University) analyze two successive polyketide synthase domains that catalyze the reduction and dehydration of the polyketide backbone during natural product biosynthesis. An article from Steven Benkovic (Pennsylvania State University) explores the biosynthetic pathway of purines and the mechanism of purinosome assembly in cells. Chengcang Wu (Intact Genomics), Nancy Keller (University of WisconsinMadison), and Neil Kelleher (Northwestern) report biosynthetic studies of the fungal nonribosomal peptide benzodiazepine benzomalvin using fungal artificial chromosomes with metabolomic scoring (FAC-MS).
■
■
KINETICS
BROAD OVERVIEWS Walter Fast’s Perspective (University of Texas, Austin) provides a classification of covalent inhibitors based on their mechanism of action. John Tanner and Donald Becker (University of Nebraska-Lincoln), along with Sarah-Maria Fendt (Leuven Cancer Institute), review the proline cycle and the role of protein metabolic enzymes in cancer metabolism. Daniel Herschlag (Stanford) reviews the nature of hydrogen bonding and its critical role in biology, drawing from a range of X-ray crystallography, NMR, and neutron diffraction data to generate some key “rules” for hydrogen bonds in biochemistry. Victor Davidson (University of Central Florida) reviews the biogenesis of protein-derived cofactors for a variety of enzyme systems. A Perspective from Chris Walsh (Stanford) and Yi Tang (University of California, Los Angeles) discusses recent developments in enzymatic cyclization reactions.
Marina Rodnina (Max Planck Institute for Biophysical Chemistry) constructs a kinetic model from FRET- and PETdependent time course data to interrogate cotranslational folding of the N5-glutamine methyltransferase HemK. Argyrides Argyrou (GlaxoSmithKline) and Luiz Pedro de Carvalho (The Francis Crick Institute) perform a steady-state kinetic based study on the bifunctional N-acetyltransferase/uridyltransferase from M. tuberculosis (GlmU). Michael Marletta (University of California, Berkeley) uses kinetic analysis to explore the mechanism in which polysaccharide monooxygenases use molecular oxygen to oxidize substrates. A Perspective by Giovanni Gadda and Pablo Sobrado (Georgia State University) recounts how kinetic solvent viscosity effects can inform the kinetic mechanism of enzymatic reactions. Nigel Richards (Cardiff University) describes the effects of hydrogen bond perturbation of Mn2+ chelating residues on the steady-state kinetics of oxalate decarboxylase. Gerardo Ferrer-Sueta (Universidad de la República) interrogates the kinetics of the
BIOSYNTHESIS Reuben Peters (Iowa State University) reports that the catalytic base pair of class II diterpene cyclases can control both the
Special Issue: Current Topics in Mechanistic Enzymology
■
© 2018 American Chemical Society
Published: June 5, 2018 3085
DOI: 10.1021/acs.biochem.8b00585 Biochemistry 2018, 57, 3085−3086
Biochemistry
Editorial
catalytic mechanism of peroxiredoxins using protein fluorescence data. A report from John Richard (University at Buffalo, SUNY) describes a kinetic analysis of various mutants of the human liver glycerol 3-phosphate dehydrogenase. Thomas Meek (Texas A&M University) details a kinetic study of cruzain, a cysteinyl protease that represents an important drug target.
monophosphate reductase. Steven Almo (Albert Einstein College of Medicine), Fahmi Himo (Stockholm University), and Frank Raushel (Texas A&M University) discuss the mechanism of γ-resorcylate decarboxylase activity using kinetic and crystallography data in combination with DFT calculations.
■
STRUCTURAL BIOLOGY Cheryl Kreinbring and Dagmar Ringe (Brandeis University) report high-resolution X-ray crystal structures of cystathionine β-synthase from S. cerevisiae. David Christianson’s Perspective (University of Pennsylvania) explores in depth the metallodeacetylase HDAC10, detailing how its structural features and reactivity distinguish it from other members of the HDAC family. Michelle Chang (University of California, Berkeley) reports the crystal structure and biochemical characterization of Acat2 and Acat5, two thiolases that are important for the biosynthesis of chemicals. Yan Jessie Zhang and Christian Whitman (University of Texas at Austin) present crystal structures for hydratase-aldolase enzymes NahE and PhdJ, which are involved in aromatic degradation pathways.
■
MECHANISM Kevin Walker (Michigan State University) uses site-directed mutagenesis to explore the active site residues involved in tyrosine aminomutase activity. Nan-Sheng Li and Joseph Piccirilli (University of Chicago) probe the transition state of HDV ribozyme catalysis via chemically modified substrates. A report from Karen Allen (Boston University) provides a detailed analysis of the human phosphomannomutase 1 enzyme, a previously uncharacterized member of the HAD superfamily. David Leys (University of Manchester) presents a detailed analysis of the NADH-dependent nonrespiratory reductive dehalogenase NpRdhA. A collaborative effort from Dan Nocera (Harvard), Marina Bennati (Max Planck Institute for Biophysical Chemistry), Cecilia Tommos (University of Pennsylvania), and JoAnne Stubbe (Massachusetts Institute of Technology) reports on the properties of 3-aminotyrosine as a probe for redox-active tyrosines in ribonucleotide reductases. Steven Schwartz (University of Arizona) and Vern Schramm (Albert Einstein College of Medicine) combine experimental and computational results to propose the role of protein vibrations as a source of catalysis in enzymes in their Perspective. A companion article from Schwartz describes a computational QM/MM study of the role of promoting vibrations in a family of artificial kemp eliminase enzymes designed using directed evolution methods. Andrew Bennet (Simon Fraser University) investigates the mechanism of a galactosidase that catalyzes hydrolysis of galactopyranosides containing fluorinated phenyl aglycones using kinetic isotope effect measurements. Dan Tawfik (Weizmann Institute of Science) examines the substrate profiles for a family of enzymes that has been shown to catalyze the formation of dimethyl sulfide (DMS) from dimethylsulfonioproprionate (DMSP). Chaitan Khosla (Stanford) shows that irreversible inhibition of transglutaminase 2 by cystamine occurs by oxidation of a pair of regulatory Cys residues, and not by modification of the active site Cys. Using 18O-labeling experiments, Emily Balskus (Harvard) delineates that the mechanism of propanediol dehydratase is distinct from that of its well-characterized relative, B12-dependent propanediol dehydratase. Reinhard Sterner (University of Regensburg) examines mutants of indole glycerol phosphate synthase to demonstrate the role of conformational flexibility in catalysis. A collaborative effort from John McCracken, Jian Hu, Bob Hausinger (Michigan State University), and Sergey Varganov (University of Nevada, Reno) uses computational, experimental, and structural studies to test two competing mechanisms for the LarA lactate racemase enzyme. Nicholas Silvaggi (University of WisconsinMilwaukee) describes the unusual reaction of oxygen with a substrate−enzyme complex catalyzed by a PLP-dependent enzyme. Hung-wen Liu (University of Texas at Austin) employs a deuterated substrate analogue to elucidate the reaction mechanism of a radical SAM lyase DesII. Mary Roberts (Boston College) and Lizbeth Hedstrom (Brandeis University) use field cycling 31P NMR to interrogate the dynamic modulation of substrates and cofactors in guanosine-5′-
John A. Gerlt,* Associate Editor, Biochemistry
■
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, United States
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
John A. Gerlt: 0000-0003-0932-5525 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
3086
DOI: 10.1021/acs.biochem.8b00585 Biochemistry 2018, 57, 3085−3086
