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Richard Honzatko

Richard Honzatko

  • Professor
  • Biochemistry, Biophysics, and Molecular Biology
The Honzatko Lab
Molecular structure is a major determinant in the expression of biochemical and physical properties of macromolecules. Quite often the three dimensional arrangement of atoms of a molecule of biological consequence provides a basis for hypothetical mechanisms of catalysis, regulation of catalysis, and the self-assembly of multisubunit proteins. Results from x-ray diffraction have contributed immensely to the understanding of hemoglobins, of allosteric enzymes such as aspartate carbamoyltransferase, of DNA, and of viral agents such as the influenza virus.

Research in Dr. Honzatko’s group focuses on the structure-function relationships of the enzymes adenylosuccinate synthetase and glucoamylase. As an enzyme governing the first commited step in AMP biosynthesis from inosine-5′-monophosphate, adenylosuccinate synthetase plays a crucial role in the metabolism of all living systems. Adenylosuccinate synthetase is important to the study of purine metabolism, to the design of drugs for chemotherapies of cancer and Chagas’ disease and to the study of fundamental aspects of chemical catalysis of reactions involving three substrates. Known inhibitors of the enzyme have potential pharmacological value. Hadacidin, for instance, has antitumor activity, selectively inhibiting denylosuccinate synthetase. L-Alanosine is converted into a metabolite, which is the most potent known inhibitor of the synthetase; that metabolite is effective also as an antitumor agent. The differences in substrate specificity of the synthetases from mammals and the synthetases from parasites responsible for Chagas’ disease (the South American sleeping sickness which afflicts some 20 million people) is a basis for the development of new drugs.

Glucoamylase from the fungus Aspergillus is perhaps the most heavily used enzyme in a commerical process. The enzyme is involved in the conversion of cornstarch to high-fructose sweeteners. The recent structure determination of glucoamylase in Dr. Honzatko’s group has provided essential information to investigators who wish to engineer an enzyme with properties better suited to its commercial application. The investigation of glucoamylase-inhibitor complexes, anticipated for the near future, should provide a wealth of information pertaining to the catalytic mechanism by which the enzyme converts starch into glucose.

Selected Publications
1: Gao Y, Iancu CV, Mukind S, Choe JY, Honzatko RB. Mechanism of Displacement of a Catalytically Essential Loop from the Active Site of Mammalian Fructose-1,6-bisphosphatase. Biochemistry. 2013 Jul 24. [Epub ahead of print] PubMed PMID: 23844654.

2: Gao Y, Honzatko RB, Peters RJ. Terpenoid synthase structures: a so far incomplete view of complex catalysis. Nat Prod Rep. 2012 Oct;29(10):1153-75. doi:10.1039/c2np20059g. Epub 2012 Aug 21. Review. PubMed PMID: 22907771; PubMed Central PMCID: PMC3448952.

3: Joseph RE, Ginder ND, Hoy JA, Nix JC, Fulton DB, Honzatko RB, Andreotti AH. Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Feb 1;68(Pt 2):145-53. doi: 10.1107/S1744309111049761. Epub 2012 Jan 25. PubMed PMID: 22297986; PubMed Central PMCID: PMC3274390.

4: Zhou K, Gao Y, Hoy JA, Mann FM, Honzatko RB, Peters RJ. Insights into diterpene cyclization from structure of bifunctional abietadiene synthase from Abies grandis. J Biol Chem. 2012 Feb 24;287(9):6840-50. doi: 10.1074/jbc.M111.337592. Epub 2012 Jan 4. PubMed PMID: 22219188; PubMed Central PMCID: PMC3307272.

Contact Info

4214 Molecular Biology Building
Social Media and Websites


  • Ph.D., Physical Chemistry, Harvard University, 1982
  • B.S., Chemistry and Mathematics, University of Michigan, 1976