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Martin K. Safo, Ph.D.


Associate Professor
Department of Medicinal Chemistry

Location:  Virginia Biotechnology Research Park, Suite 212
Phone: (804) 828-7291
Email: msafo@vcu.edu

Mailing Address

Virginia Biotech I
800 E. Leigh St.
P.O. Box 980540
Richmond, VA 23219-1540
Fax: (804) 827-3664


Education

  • B.S., Chemistry (University of Cape Coast, Ghana, 1985)
  • Ph.D., Inorganic Chemistry/X-ray Crystallography (University of Notre Dame, 1991)

Post-Graduate Training

  • Postdoc - Sickle Cell Disease (Virginia Commonwealth University, 1991)
  • Research Associate - Macromolecule X-ray Crystallography (Academia Sinica, Taipei, Taiwan, 1994)

Academic Appointments/Professional Experience

  • (2010 - Present) Associate Professor, Virginia Commonwealth University
  • (1998 - 2010) Assistant Professor, Virginia Commonwealth University

Research Interests

  • My primary research interest focuses on structure-function studies of enzymes involved in vitamin B6 metabolism, regulation and utilization. Pyridoxal 5’-phosphate (PLP), the active form of vitamin B6 serves as a cofactor for over 140 vitamin B6-dependent enzymes involved in amino acid, sugar, and neurotransmitter metabolisms. Pyridoxine 5’-phosphate oxidase (PNPOx) and pyridoxal kinase (PL kinase) are the two key enzymes that supply PLP to these B6 enzymes by both the salvage pathway and the conversion of nutritional sources of vitamin B6. Deficiency of PLP has been linked to several neurological symptoms, as well as a number of psychiatric disorders. Through a combination of kinetics, site-directed mutagenesis, and structural studies, we have elucidated the catalytic mechanisms of PNPOx and PL kinase. The present goal is to gain insight into the mechanism of PLP regulation and subsequent transfer to dozens of apo-B6 enzymes.
  • Another research interest involves structure-function studies of hemoglobin and rational design of antisickling agents. Sickle cell disease (SCD) is a hereditary blood disorder, affecting over 75,000 people in the United States and millions of people worldwide. In SCD, a mutation in the ß-globin protein of hemoglobin causes deoxygenated sickle hemoglobin to form insoluble polymers inside red blood cells which deform into rigid shapes or sickle red blood cells that occlude capillaries and small blood vessels. The overall goal of this project is to use structure-based drug design, including X-ray crystallography, molecular modeling, synthesis, and biological evaluation to discover hemoglobin allosteric effectors and/or covalent modifiers that may be useful for treating SCD. A second goal is to use X-ray crystallography to unravel the allosteric switch mechanism of hemoglobin.

Publications

PubMed Search
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  • Patents
    • M. K. Safo, R. Danso-Danquah, S. S. Nokuri, F. N. Musayev, G. S. Joshi, J. C. Burnett, and D. J. Abraham. Antisickling Agents. US Patent No. 7160910, 2007.
    • M. K. Safo, R. Danso-Danquah, G. S. Joshi, and D. J. Abraham. Antisickling Agents. US Patent No. 7,119,208 B2, 2006.
    • D. J. Abraham, G. S. Joshi, S. J. Hoffman, M. Grella, R. Danso-Danquah, A. Yousseff, M. K. Safo, S. Kulkarni. "Substituted Chiral Allosteric Hemoglobin Modifiers". US Patent No. 6,486,342 B1, 2002.
    • D. J. Abraham, M. K. Safo, T. Boyiri, and R. E. Danso-Danquah. "Aldehydic Agents for Allosteric Modification of Hemoglobin". US Patent No. 5,599,974, 1997.
  • Recent Publications
    • 1.F. N. Musayev, M. Di Salvo, M. Saveedra, R. Contestabile, M. S. Ghatge, V. Schirch, M. K. Safo. “Crystal structure of human pyridoxine 5'-phosphate oxidase mutant R229W: Structural basis for reduced PNP Oxidase catalytic activity in neonatal epileptic encephalopathy disorder” J. Biol. Chem. 2009.
    • 2.A.K. Gandhi, M.S. Ghatge, F.N. Musayev, A. Sease, S.O.Aboagye, M.L. di Salvo, V. Schirch, and M. K. Safo. “Kinetic and structural studies of the role of the active site residue Asp235 of human pyridoxal kinase”. Biochem. Biophys. Res. Commun., 2009.
    • 3.J. D. Jenkins, F.N. Musayev, R. Danso-Danquah, D.J. Abraham, M. K. Safo. “Structure of relaxed-state human hemoglobin: insight into ligand uptake, transport and release.” Acta Crystallogr D. 2009, 65: 41-48.
    • 4.I. N. Nnamani, G. S. Joshi, R. Danso-Danquah, O. Abdulmalik, T. Asakura, D. J. Abraham, and M. K. Safo. “Pyridyl Derivatives of Benzaldehyde as Potential Antisickling Agents.”Chemistry & Biodiversity, 2008 5:1762-1769.
    • 5.J. Yi, M. K. Safo, and G. B. Richter-Addo. “The Nitrite Anion Binds to Human Hemoglobin via the Uncommon O-Nitrito Mode.” Biochemistry, 2008, 47: 8247-8249.
    • 6. F. N. Musayev, M. L. di Salvo, T.-P. Ko, A. K. Gandhi, A. Goswami, V. Schirch, and M. K. Safo. “Crystal Structure of human pyridoxal kinase: Structural basis of M+ and M2+ activation.” Protein Sci., 2007, 16: 2184-2194.
    • 7. M. K. Safo, F. N. Musayev, M. di Salvo, S. Hunt, and V. Schirch. “Crystal Structure of Pyridoxal Kinase from the Escherichia coli PdxK gene: Implications for the Classification of Pyridoxal Kinases.” J. Bacteriol. 2006, 4542-4552.
    • 8. M. K. Safo and D. J. Abraham. “The Enigma of the Liganded Hemoglobin End-State: A Novel Quaternary Structure of Human Carbonmonoxy Hemoglobin.” Biochemistry, 2005, 44, 8347-8359.
    • 9. O. Abdulmalik, M. K. Safo, N.B. Lerner, J. Ochotorena, E. Daikhin, V. Lakka, R. Santacroce, D. J. Abraham and T. Asakura. “5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells.” Br. J. Hematol. 2005,128, 552-561