Genbin Shi, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 538, Room 116
- Frederick, MD 21702-1201
- 301-846-5348
- shigenbin@mail.nih.gov
RESEARCH SUMMARY
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
Genbin Shi, Ph.D.
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.
Publications
Structural enzymology and inhibition of the bi-functional folate pathway enzyme HPPK-DHPS from the biowarfare agent Francisella tularensis
Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties
Bisubstrate analog inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: new lead exhibits a distinct binding mode
New ways to derivatize at position 6 of 7,7-dimethyl-7,8-dihydropterin
Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies
Biography
Genbin Shi, Ph.D.
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.