William R Montfort, PhD

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Professor, Chemistry and Biochemistry-Sci
Professor, BIO5 Institute
Professor, Molecular and Cellular Biology
Professor, Applied Mathematics - GIDP
Professor, Cancer Biology - GIDP
Professor, Genetics - GIDP
Biography
William Montfort received BS and PhD degrees in Chemistry (Biochemistry emphasis) from Oakland University (1980) and the University of Texas (1985). His graduate studies, with Prof. Jon Robertus, led to the crystal structure of ricin. In his postdoctoral studies, with Prof. Robert Stroud at the University of California, San Francisco, he determined crystal structures of anticancer drug target thymidylate synthase. He moved to the University of Arizona in 1989, where he established a laboratory focused on protein structure/function and founded the X-ray crystallography facility. He is now Professor of Chemistry and Biochemistry, and Director of the NIH-funded Biological Chemistry Graduate Program.
Cancer Focus
My research broadly concerns the link between protein structure and protein function, including how ligands and drugs bind to their targets and influence activity. One focus concerns nitric oxide signaling, with an emphasis on nitric oxide driven breast cancer. Our work includes studies on NO binding, transport and signaling regulation, and our approaches span atoms to animals. Among our studies are crystal structures of proteins containing nitrosyl-heme or nitroso-cysteine, transient kinetic measurements, biophysical measurements of transmembrane complexes and functional measurements in live cells. We currently seek mechanistic understanding of how excess nitric oxide production in breast cancer drives an aggressive tumor phenotype, and have identified novel targets for therapeutic intervention.
Selected Publications
Weichsel, A., J. A. Kievenaar, R. Curry, J. T. Croft, and W. R. Montfort, "Instability in a coiled-coil signaling helix is conserved for signal transduction in soluble guanylyl cyclase.", Protein Sci, vol. 28, issue 10, pp. 1830-1839, 2019 10. PMCID: PMC6739824 PMID: 31411784
Fritz, B. G., S. A. Roberts, A. Ahmed, L. Breci, W. Li, A. Weichsel, J. L. Brailey, V. H. Wysocki, F. Tama, and W. R. Montfort, "Molecular model of a soluble guanylyl cyclase fragment determined by small-angle X-ray scattering and chemical cross-linking.", Biochemistry, vol. 52, issue 9, pp. 1568-82, 2013 Mar 05. PMCID: PMC3607398 PMID: 23363317
Hu, X., C. Feng, J. T. Hazzard, G. Tollin, and W. R. Montfort, "Binding of YC-1 or BAY 41-2272 to soluble guanylyl cyclase induces a geminate phase in CO photolysis.", J Am Chem Soc, vol. 130, issue 47, pp. 15748-9, 2008 Nov 26. PMCID: PMC2645941 PMID: 18980304
Weichsel, A., E. M. Maes, J. F. Andersen, J. G. Valenzuela, T. Kh Shokhireva, A. F Walker, and W. R. Montfort, "Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein.", Proc Natl Acad Sci U S A, vol. 102, issue 3, pp. 594-9, 2005 Jan 18. PMCID: PMC545542 PMID: 15637157
Weichsel, A., J. F. Andersen, S. A. Roberts, and W. R. Montfort, "Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial.", Nat Struct Biol, vol. 7, issue 7, pp. 551-4, 2000 Jul. PMID: 10876239