# positions[].organizations[].parent[].label
College of Agriculture and Life Sciences

# overview
Marketed drugs have been developed for representatives of all six classes of enzymes, and comprise essential therapies for the treatment of cancers, HIV/AIDS, hypercholesterolemia, and bacterial infections. The availability of known point mutations that are causative of human cancers , as well as the full genomic descriptions of many pathogens, such as parasitic protozoa and infectious bacteria, provides an emerging means to identify new or known enzymes that would constitute potential drug targets. Likewise, the availability of crystal structures of many of these enzymes or their analogues, provides a means to rationally design new inhibitors of enzyme drug targets via the use of molecular modelling and a full understanding of the chemical mechanism of the target enzymes, as an important adjuvant to inhibitor discovery via high-throughput screening.

Our laboratory will initially focus on the detailed study of the mechanisms of cysteine proteases such as cathepsin C, the isocitrate lyase of Mycobacterium tuberculosis, and human ATP-citrate lyase, by the use of pre-steady-state and steady-state kinetics, as well as by use of existing crystal structures of these enzymes, to inform the design of both covalent and other mechanism-based modes for the inactivation of these enzymes. We will design and synthesize candidate inhibitors, and test them against these and other enzyme targets, and determine their suitability as potential drug candidates.

# keywords[]
5 Development Of Treatments And Therapeutic Interventions

# keywords[]
5 Development Of Treatments And Therapeutic Interventions

# educationAndTraining[].organization.label
Pennsylvania State University - (State College, Pennsylvania, United States)

# educationAndTraining[].organization.label
University of Virginia - (Charlottesville, Virginia, United States)

# publications[].label
Drug-target residence time and its implications for lead optimization.

# publications[].label
The amino-acid substituents of dipeptide substrates of cathepsin C can determine the rate-limiting steps of catalysis.

# publications[].label
Catalytic Mechanism of Cruzain from Trypanosoma cruzi As Determined from Solvent Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.

# publications[].label
Human immunodeficiency virus-1 protease. 1. Initial velocity studies and kinetic characterization of reaction intermediates by 18O isotope exchange.

# publications[].label
Kinetic mechanism of Escherichia coli glutamine synthetase.

# publications[].label
Use of protein unfolding studies to determine the conformational and dimeric stabilities of HIV-1 and SIV proteases.

# publications[].label
Inhibition of human immunodeficiency virus 1 protease in vitro: rational design of substrate analogue inhibitors.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
HIV-1 protease as a potential target for anti-AIDS therapy.

# publications[].label
Escherichia coli glutamine synthetase. Determination of rate-limiting steps by rapid-quench and isotope partitioning experiments.

# publications[].label
Mechanistic enzymology in drug discovery: a fresh perspective.

# publications[].label
Purification, characterization, and kinetic analysis of inosine 5'-monophosphate dehydrogenase of Tritrichomonas foetus.

# publications[].label
An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis.

# publications[].label
Mechanism of inhibition of cathepsin K by potent, selective 1, 5-diacylcarbohydrazides: a new class of mechanism-based inhibitors of thiol proteases.

# publications[].label
Purification and biochemical characterization of recombinant simian immunodeficiency virus protease and comparison to human immunodeficiency virus type 1 protease.

# publications[].label
Human immunodeficiency virus 1 protease expressed in Escherichia coli behaves as a dimeric aspartic protease.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Rational design, synthesis, and crystallographic analysis of a hydroxyethylene-based HIV-1 protease inhibitor containing a heterocyclic P1'--P2' amide bond isostere.

# publications[].label
Development of a high-throughput screen to detect inhibitors of TRPS1 sumoylation.

# publications[].label
Carbamoyl-phosphate synthetase II of the mammalian CAD protein: kinetic mechanism and elucidation of reaction intermediates by positional isotope exchange.

# publications[].label
Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry.

# publications[].label
Nonpeptide HIV protease inhibitors designed to replace a bound water

# publications[].label
Solvent isotope partitioning: a new kinetic tool for the determination of desorption rates of reactant water from enzyme-substrate complexes in proteases.

# publications[].label
Kinetic and chemical mechanisms of the fabG-encoded Streptococcus pneumoniae beta-ketoacyl-ACP reductase.

# publications[].label
Will nanomedicine deliver on its promise of changing therapeutics or remain an interesting and important research tool in cell biology and physiology?

# publications[].label
Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Chromophoric peptide substrates for the spectrophotometric assay of HIV-1 protease.

# publications[].label
Synthetic Inhibitors of HIV1 Protease Block Processing of Pr55gag and Pr160gagpo1 Polyproteins in Infected T Lymphocytes

# publications[].label
Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease.

# publications[].label
Peptide substrates and inhibitors of the HIV-1 protease.

# publications[].label
Identification of a novel aspartic protease (Asp 2) as beta-secretase.

# publications[].label
Erratum: Drugtarget residence time and its implications for lead optimization

# publications[].label
ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site.

# publications[].label
Human immunodeficiency virus-1 protease. 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism.

# publications[].label
Synthesis and antiviral activity of a novel class of HIV-1 protease inhibitors containing a heterocyclic P1-P2 amide bond isostere

# publications[].label
Understanding the origins of time-dependent inhibition by polypeptide deformylase inhibitors.

# publications[].label
4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.

# publications[].label
Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues.

# publications[].label
Human immunodeficiency virus type 1 protease inhibitors irreversibly block infectivity of purified virions from chronically infected cells.

# publications[].label
On the catalytic mechanism of human ATP citrate lyase.

# publications[].label
Use of nitrogen-15 kinetic isotope effects to elucidate details of the chemical mechanism of human immunodeficiency virus 1 protease.

# publications[].label
Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis.

# publications[].label
Novel receptor antagonists welcome a new era in endothelin biology.

# publications[].label
Characterization and autoprocessing of precursor and mature forms of human immunodeficiency virus type 1 (HIV 1) protease purified from Escherichia coli.

# publications[].label
Proteolysis of an active site peptide of lactate dehydrogenase by human immunodeficiency virus type 1 protease.

# publications[].label
Adaptation of the plasma renin radioimmunoassay for use with HIV-1 protease.

# publications[].label
Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the gag precursor.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays.

# publications[].label
Enhanced Antibiotic Discovery by PROSPECTing.

# publications[].label
Chemical mechanism of a cysteine protease, cathepsin C, as revealed by integration of both steady-state and pre-steady-state solvent kinetic isotope effects.

# publications[].label
Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.

# publications[].label
Inactivation of HIV-1 protease by a tripeptidyl epoxide

# publications[].label
Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Steady-state kinetic characterization of substrates and metal-ion specificities of the full-length and N-terminally truncated recombinant human methionine aminopeptidases (type 2).

# publications[].label
Use of steady state kinetic methods to elucidate the kinetic and chemical mechanisms of retroviral proteases.

# publications[].label
Kinetic mechanism and rate-limiting steps of focal adhesion kinase-1.

# publications[].label
A symmetric inhibitor binds HIV-1 protease asymmetrically.

# researcherOn[].label
Novel Inhibitors of Cruzain and Trypanosoma brucei Cathepsin B as Potential Drug Candidates for the treatment of African Trypanosomiasis and Chagas Disease

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].label
Rational design of enzyme inhibitors as potential drugs to treat tuberculosis, malaria, African sleeping sickness, and Chagas disease.

# researcherOn[].awardedBy.label
National Institute of Food and Agriculture - (Washington D.C., District of Columbia, United States)

# researcherOn[].label
Evaluation of Trk Probes in Models for Dry Eye Disease

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].label
Protozoan Purine Phosphoribosyltransferases as Targets to Treat Malaria, African Trypanosomiasis and Chagas's Disease

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Allergy and Infectious Diseases

# streetAddress
Texas A&M University; Biochemistry & Biophysics; 2128 TAMU

# organizations[]
College of Agriculture and Life Sciences

# schools[]
College of Agriculture and Life Sciences

# inTheNews[].label
Texas A&M chemists working on drugs to treat COVID-19

# inTheNews[].label
Texas A&M Researchers Lead Study Of COVID-19 Blocking Enzyme

# inTheNews[].label
Chemists working on drugs to treat COVID-19