Genbin Shi, Ph.D.
Genbin Shi, Ph.D.
Staff Scientist

Dr. Shi's current research focuses on the inhibitor design and synthesis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK). HPPK catalyzes magnesium-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin.  It is a key enzyme in the folate biosynthetic pathway, essential for microorganisms but absent from mammals.  Therefore, HPPK is an attractive target for developing novel antimicrobial agents.

As Staff Scientist, Dr. Shi plays a leading role in the Section’s drug development efforts, including structure-based design and synthesis of antimicrobial, anticancer, and anti-AIDS agents. 

Areas of Expertise
1) structure-based drug design, 2) structural biology, 3) chemical biology, 4) medicinal chemistry, 5) folate pathway.

Contact Info

Genbin Shi, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 538, Room 208
Frederick, MD 21702-1201
301-846-5348
shigenbin@mail.nih.gov

Dr. Shi's current research focuses on the inhibitor design and synthesis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK). HPPK catalyzes magnesium-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. It is a key enzyme in the folate biosynthetic pathway, essential for microorganisms but absent from mammals.  Therefore, the enzyme is an attractive target for developing novel antimicrobial agents. Using structure-based approach, a family of linked purine pterin HPPK inhibitors has been designed, synthesized, and characterized for the development of novel antibacterial agents.

Scientific Focus Areas:
Cancer Biology, Chemical Biology, Microbiology and Infectious Diseases, Molecular Biology and Biochemistry, Structural Biology
Selected Key Publications
  1. Shaw GX, Li Y, Shi G, Wu Y, Cherry S, Needle D, Zhang D, Tropea JE, Waugh DS, Yan H, Ji X.
    FEBS J. 281(18): 4123-37, 2014. [ Journal Article ]
  2. Shi G, Shaw G, Liang YH, Subburaman P, Li Y, Wu Y, Yan H, Ji X.
    Bioorg Med Chem. 20(1): 47-57, 2012. [ Journal Article ]
  3. Shi G, Shaw G, Li Y, Wu Y, Yan H, Ji X.
    Bioorg Med Chem. 20(14): 4303-9, 2012. [ Journal Article ]
  4. Shi G, Ji X.
    Tetrahedron Lett. 52(46): 6174-6176, 2011. [ Journal Article ]
  5. Shi G, Blaszczyk J, Ji X, Yan H.
    J Med Chem. 44(9): 1364-71, 2001. [ Journal Article ]

Dr. Shi received his Ph.D. in organic chemistry and medicinal chemistry from Shanghai Institute of Materia Medica, Chinese Academy of Sciences in 1995, under the supervision of Professor Kaixian Chen and Professor Ruyun Ji. He received postdoctoral training in the laboratory of Professor Honggao Yan at Michigan State University from 1997 to 2000, working  on the structure-and-function relationship of folate pathway enzymes using protein chemistry, NMR, and other biophysics techniques. He then received training in molecular and cell biology in the laboratory of Professor Mark de Caestecker at Vanderbilt University, where he carried out functional studies of the CITED1 (CBP/p300-interacting transactivators with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain) protein. In 2008, Dr. Shi joined the Macromolecular Crystallography Laboratory.

Research

Dr. Shi's current research focuses on the inhibitor design and synthesis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK). HPPK catalyzes magnesium-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. It is a key enzyme in the folate biosynthetic pathway, essential for microorganisms but absent from mammals.  Therefore, the enzyme is an attractive target for developing novel antimicrobial agents. Using structure-based approach, a family of linked purine pterin HPPK inhibitors has been designed, synthesized, and characterized for the development of novel antibacterial agents.

Scientific Focus Areas:
Cancer Biology, Chemical Biology, Microbiology and Infectious Diseases, Molecular Biology and Biochemistry, Structural Biology

Publications

Selected Key Publications
  1. Shaw GX, Li Y, Shi G, Wu Y, Cherry S, Needle D, Zhang D, Tropea JE, Waugh DS, Yan H, Ji X.
    FEBS J. 281(18): 4123-37, 2014. [ Journal Article ]
  2. Shi G, Shaw G, Liang YH, Subburaman P, Li Y, Wu Y, Yan H, Ji X.
    Bioorg Med Chem. 20(1): 47-57, 2012. [ Journal Article ]
  3. Shi G, Shaw G, Li Y, Wu Y, Yan H, Ji X.
    Bioorg Med Chem. 20(14): 4303-9, 2012. [ Journal Article ]
  4. Shi G, Ji X.
    Tetrahedron Lett. 52(46): 6174-6176, 2011. [ Journal Article ]
  5. Shi G, Blaszczyk J, Ji X, Yan H.
    J Med Chem. 44(9): 1364-71, 2001. [ Journal Article ]

Biography

Dr. Shi received his Ph.D. in organic chemistry and medicinal chemistry from Shanghai Institute of Materia Medica, Chinese Academy of Sciences in 1995, under the supervision of Professor Kaixian Chen and Professor Ruyun Ji. He received postdoctoral training in the laboratory of Professor Honggao Yan at Michigan State University from 1997 to 2000, working  on the structure-and-function relationship of folate pathway enzymes using protein chemistry, NMR, and other biophysics techniques. He then received training in molecular and cell biology in the laboratory of Professor Mark de Caestecker at Vanderbilt University, where he carried out functional studies of the CITED1 (CBP/p300-interacting transactivators with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain) protein. In 2008, Dr. Shi joined the Macromolecular Crystallography Laboratory.