个人简介

Professor Holz earned his bachelor’s degree at Bemidji State University, his master’s degree at the University of Minnesota-Duluth and his doctorate in chemistry from The Pennsylvania State University. He was a National Institutes of Health Postdoctoral Research Fellow at the University of Minnesota after which he joined the faculty at Utah State University before moving to Loyola University Chicago as the Chair of the Chemistry Department, before moving to Marquette. He has contributed to more than 90 research articles and co-invented two patents.

研究领域

Inorganic Chemistry and Biochemistry

The Holz research group interfaces the general areas of inorganic chemistry, mechanistic enzymology and biophysical chemistry. In general the Holz group is interested in structure/function studies of metalloenzymes some of which are antimicrobial targets. Within these studies, the Holz group uses a wide variety of biochemical and biophysical methods such as enzyme kinetics, site-directed mutagenesis, isothermal titration calorimetry, UV-Vis, NMR and EPR spectroscopies. Current projects in the Holz group center on an NSF sponsored project to study the catalytic mechanism of nitrile hydratases (NHases) and an NIH sponsored project to study the zinc dependent dapE-encoded desuccinylase from Haemophilus influenzae (DapE). NHases are metalloenzymes in the nitrile degradation pathway that catalyze the hydration of nitriles to their corresponding amides at ambient pressures and temperatures at physiological pH. NHases have attracted substantial interest as biocatalysts in preparative organic chemistry and are used in many applications such as the large scale industrial production of acrylamide and nicotinamide. Because of their exquisite reaction specificity, the nitrile-hydrolyzing potential of NHase enzymes is becoming increasingly recognized as a truly new type of “Green” chemistry. However, little is understood about how NHase enzymes function. Therefore, a better understanding of the structure and reaction mechanism of NHase enzymes will enable access to nitrile-hydrolyzing materials with broader substrate ranges, higher activities, and greater stabilities. DapE is a member of the lysine biosynthetic pathway, which also produces meso-diaminopimelic acid (meso-DAP), an essential component of bacterial cell wall synthesis. Disruption of the biosynthesis of meso-DAP has been shown to result in cell death for several bacteria. Since drug resistance in pathogenic bacteria has increased tremendously in the past few years, DapE’s are potential novel pharmaceutical targets for which a human counterpart does not exist. Therefore, the design and synthesis of small molecules that inhibit DapE may lead to a new class of antibiotics.

近期论文

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Gumtaotao, Natalie; Kuhn, Misty L.; Hajnas, Natalia; Holz*, Richard C. “Identification of an Active Site Bound Nitrile Hydrotase Intermediate Through Single Turnover Stopped-Flow Spectroscopy” J. Biol. Chem., 2013, 288 15532-6. Gilner, Danuta M.; Becker, Daniel; Holz*, Richard C. “Lysine Biosynthesis in Bacteria: A Metallodesuccinylase as a Potential Antimicrobial Target” J. Biol. Inorg. Chem., 2013, 155-163. Tao, Ye; Shokes, Jacob E.; McGregor, Wade C.; Scott, Robert A.; Holz*, Richard C. “Structural Characterization of Zn(II)-, Co(II)-, and Mn(II)-Loaded forms of the argE-Encoded N-Acetyl-L-Ornithine Deacetylase from Escherichia coli” J. Inorg. Biochem., 2012, 111, 157–163. Kuhn, Misty L.; Martinez, Salette; Gumataotao, Natalie; Bornscheuer, Uwe; Liu, Dali; Holz*, Richard C. "The Fe-Type Nitrile Hydratase from Comamonas testosteroni Ni1 Does Not Require an Activator Accessory Protein for Expression in E. Coli" Biochem. Biophys. Res. Comm., 2012, 422, 365-370. Osner, Zachary; Nyamjav, Dorjderem; Holz*, Richard C.; Becker*, Daniel “Direct Patterning of a Cyclotriveratrylene (CTV) Derivative on for Directed Self-Assembly of C60” Nanotech., 22, 2011, 275611. Hlaváček*, Jan; Pícha, Jan; Vaněk, V.; Jiráček, J.; Slaninová, J.; Fučík, V.; Buděšínský, M.; Gilner, Danuta M.; Holz*, Richard C. "Inhibitors of Nα-Acetyl-L-Ornithine Deacetylase (ArgE) as New Antimicrobial Agents: Synthesis and Characterization" Amino Acids, 2010, 38, 1155–1164. Vaněk, V.; Pícha, Jan; Buděšínský, Miloš; Šanda, Miloslav; Jiráček, J.; Holz*, Richard C.; Hlaváček*, Jan "Synthesis of N-succinyl-l,l-Diaminopimelic Acid Mimetics via Asymmetric Protection" Prot. Pept. Lett., 2010, 17, 405-409. Nocek, Boguslaw P.; Gilner, Danuta M.; Fan, Yao; Holz*, Richard C.; Joachimiak*, Andrzej “X-ray Crystal Structures of the Mono and Di-Zinc forms of the dapE-encoded N-succinyl-L,L-Diaminopimelic Acid Desuccinylase from Haemophilus influenzael Provides a Structural Basis for Catalysis by both the Mono and Dimetalated Enzymes” J Mol. Biol., 2010, 397, 617-626. Nyamjav, Dorjderem; Sergey Rozhok; Osner, Zachary; Holz*, Richard C. “Immobilization of Motile Bacterial Cells via Dip-Pen Nanolithography" Nanotech., 21, 2010, 235105. Frey*, Steven T.; Guilmet, Stephanie L.; Egan, Richard G.; Bennett, Alyssa; Holz*, Richard C. “Immobilization of the Aminopeptidase from Aeromonas Proteolytica on Mg2+/Al3+ Layered Double Hydroxide Particles” ACS Appl. Mater. Interfaces, 2010, 2, 2828-2832. Nyamjav, Dorjderem; Holz*, Richard C. “Direct Paterning of Silanized-Biomolecules on Semiconductor Surfaces” Langmuir, 2010, 26, 18300-18302. Gilner, Danuta M.; Bienvenue, David; Nocek, Boguslaw P.; Joachimiak, Andrzej; Zachary, Vincentos; Bennett*, Brian; Holz*, Richard C. “The dapE-encoded N-succinyl-L,L-Diaminopimelic Acid Desuccinylase from Haemophilus influenzae Contains two Active Site Histidine Residues” J. Biol. Inorg. Chem., 2009, 14, 1-10. Mitra, Sanghamitra; Bennett*, Brian; Holz*, Richard C. "Mutation of H63 and its Catalytic Effect on the Methionine Aminopeptidase from Escherichia coli” Biochim. Biophys. Acta, 2009, 1794, 137-143. Mitra, Sanghamitra; Sheppard, George; Wang, Jieyi; Bennett*, Brian; Holz*, Richard C “Analyzing the Binding of Co(II)-Specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus” J. Biol. Inorg. Chem., 2009, 14, 573-585. Gilner, Danuta M.; Holz*, Richard C.; Becker*, Daniel “Inhibitors of Bacterial N-Succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of in vitro Antimicrobial Activity” Bioorg. Med. Chem. Lett., 2009, 19, 6350-6352.