Dr. Richard C. HolzMarquette University
Sensenbrenner Hall, 102MilwaukeeWI53201United States of America(414) email@example.com
Klingler College of Arts and Sciences
Dr. Richard C. Holz is the dean of the Helen Way Klingler College of Arts and Sciences.
Prior to joining Marquette, Holz was a faculty member for seven years at Loyola University Chicago. During his term at Loyola, he served as associate dean for resources and planning in the College of Arts and Sciences (2011–2013) and as department chairman of the chemistry and biochemistry department (2006–2011). He was an American Council on Education Fellow (Class of 2010–2011).
Holz has a bachelor’s degree from Bemidji State University, a master’s degree from the University of Minnesota–Duluth and a doctorate from The Pennsylvania State University, all in chemistry. He was a National Institutes of Health postdoctoral research fellow at the University of Minnesota from 1989–1992 and a faculty member at Utah State University from 1992–2006.
Holz is a bioinorganic chemist and is interested in structure/function studies of metalloenzymes, which includes the design, synthesis and characterization of small molecules that function as potent inhibitors. He has published more than 100 research articles. His research program is currently funded by the National Science Foundation.
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.
- 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 viaAsymmetric 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.
National Science Foundation- (CHE-1058357)7/1/2011 to 6/30/2014, “Collaborative Research on the Catalytic Mechanism of Nitrile Hydration Catalysts” The goals of this proposal are to elucidate the mechanism of nitrile hydration by NHase and to ascertain the generality of the mechanism by comparison of three distinct NHases. These studies will inform the design of reaction conditions for the use of NHase as an industrial biocatalyst for organic chemical processing, industrial synthesis, and bioremediation. In addition, successful completion of the work will inform the design of synthetic nitrile hydrating catalysts with tailored catalytic properties. An interdisciplinary approach will be used that incorporates kinetic, spectroscopic, biochemical, and X-ray crystallographic methods
National Institutes of Health – (R15 AI085559-01A1) 5/1/2010 to 4/30/2014, "A New Antibacterial Drug Target: Analyzing Inhibitor Binding to a Bacterial Metallohydrolase” the hypothesis of this proposal is that highly potent inhibitors of enzymes in the mDAP/lysine biosynthetic pathway will provide a previously undescribed class of antibacterials. It has been shown that deletion of the gene encoding for DapE is lethal to Helicobacter pyloriand Mycobacterium smegmatis indicating that DapE's are essential for cell growth and proliferation. Therefore, the goal of this proposal is to discover new antimicrobial lead compounds for DapE enzymes and analyze the determinants of substrate/inhibitor binding.