Yi Jin, Ph.D.
Yi Jin, Ph.D.
Research Assistant Professor of Pharmacology
Department: Pharmacology
Contact information
Department of Pharmacology
Room 135
John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104-6084
Room 135
John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104-6084
Office: 215.898.1144
Fax: 215.573.7188
Fax: 215.573.7188
Email:
jinyi@mail.med.upenn.edu
jinyi@mail.med.upenn.edu
Education:
MS (Protein Crystallography)
Beijing University, 1993.
PhD (Biological Chemistry)
University of Minnesota, 2000.
Permanent linkMS (Protein Crystallography)
Beijing University, 1993.
PhD (Biological Chemistry)
University of Minnesota, 2000.
Description of Research Expertise
The general interests of Dr. Jin's research lie in the study of structure/function of enzymes and their involvement in human diseases, particularly in the study of enzymes involved in steroid biosynthesis and metabolism.1. Structure and Function of Steroid Transform Enzymes of the Aldo-Keto Reductase (AKR) Family and Their Role in Steroid Metabolism
Steroid transforming AKRs play important roles in systemic steroid metabolism and regulate the levels of active hormones in target tissues. The kinetic behavior, substrate recognition, and stereospecificity of these enzymes are studied by a combination of biochemical and structural approaches, such as steady state and transient state kinetics, crystallography, and molecular modeling.
2. Role of AKR in Synthetic Steroid Hormone Metabolism and Action
Role of AKR in pharmacological effects of synthetic glucocorticoids for asthma (i.e., systemic side-effects and drug resistance) and the cardiovascular effects of progestins in hormonal therapy for women are studied by characterizing enzyme and cell-based steroid metabolism, enzyme inhibition, hormone receptor activity, and enzyme expression levels in relevant cells, etc.
3. Function of Cytochrome P450 NADPH Oxidoreductase (POR) Genetic Variants
POR provides electrons for the catalysis of all 50 human microsomal P450 enzymes which include the hepatic drug-metabolizing and the steroidogenic enzymes. POR genetic variants, which include disease causing mutations and SNPs from the normal population, have been shown to affect the activities of different P450s in vitro. Effects of POR mutations/polymorphisms on the electron transfer properties of the enzyme (i.e., inter molecule transfer from NADPH, intra molecule transfer between FAD and FMN components, and inter molecule transfer to different P450 acceptors) are investigated by stopped-flow spectroscopy.
Selected Publications
Jin Y, Mesaros CA, Blair IA, Penning TM: Stereospecific reduction of 5β-reduced steroids by human ketosteroid reductases of the aldo-keto reductase (AKR) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5β-reductase pathway. Biochem J April 26 2011 [Epub ahead of print]Jin Y: Activities of aldo-keto reductase 1 enzymes on two inhaled corticosteroids: Implications for the pharmacological effects of inhaled corticosteroids. Chem Biol Interact Jan 27 2011 [Epub ahead of print]
Adeniji AO, Twenter BM, Byrns MC, Jin Y, Winkler JD, Penning TM: Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3). Bioorg Med Chem Lett 21(5): 1464-1468, 2011.
Byrns MC, Jin Y, Penning TM [co-first author]: Inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3): Overview and structural insights. J Steroid Biochem Mol Biol Nov 16 2010 [Epub ahead of print]
Penning TM, Lee SH, Jin Y, Gutierrez A, Blair IA: Liquid chromatography-mass spectrometry (LC-MS) of steroid hormone metabolites and its applications. J Steroid Biochem Mol Biol 121(3-5): 546-555, 2010.
Jin Y, Duan L, Lee S-H, Kloosterboer HJ, Blair IA, Penning TM: Human cytosolic hydroxysteroid dehydrogenases of the aldo-ketoreductase superfamily catalyze reduction of conjugated steroids: implications for phase I and phase II steroid hormone metabolism. J Biol Chem 284(15): 10013-10022, 2009.
Penning TM, Jin Y, Rizner TL, Bauman DR: Pre-receptor regulation of the androgen receptor. Mol Cell Endo 281(1-2): 1-8, 2008.
Cooper WC, Jin Y, Penning TM [co-first author]: Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: The example of rat liver 3alpha-HSD (AKR1C9). J Biol Chem 282(46): 33484-33493, 2007.
Jin Y, Penning TM: Multiple steps determine the overall rate of the reduction of 5alpha-dihydrotestosterone catalyzed by human type 3 3alpha-hydroxysteroid dehydrogenase: implications for the elimination of androgens. Biochemistry 45(43): 13054-1363, 2006.
Jin Y, Penning TM: Molecular docking simulations of steroid substrates into human cytosolic hydroxysteroid dehydrogenases (AKR1C1 and AKR1C2): Insights into positional and stereochemical preferences. Steroids 71(5): 380-391, 2006.