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Faculty Profile

Emmanuel S. Burgos, Ph.D.

Dr. Emmanuel S. Burgos
 

Professional Interests

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first reversible step in NAD biosynthesis and nicotinamide (NAM) salvage (Figure 1, A – red). The enzyme is designed for efficient capture of nicotinamide by energetic coupling of ATP hydrolysis to assist in extraordinary NAM binding affinity[3] and formation of nicotinamide mononucleotide (NMN,. NAMPT provides the mechanism to replenish the NAD pool in human metabolism. In addition to its role in redox biochemistry, NAD fuels the sirtuins (SIRTs) to regulate transcription factors involved in pathways linked to inflammation, diabetes and lifespan (Figure 1, B – pink).

 

NAMPT-mediated lifespan expansion has caused a focus on the catalytic mechanism, regulation and inhibition of NAMPT. Structural, mechanistic and inhibitor design all contribute to a developing but yet incomplete story of NAMPT function. Although the first generation of NAMPT inhibitors has entered clinical trials, disappointing outcomes suggest more powerful and specific inhibitors will be needed.

 

Understanding the ATP-linked mechanism of NAMPT and the catalytic site machinery may permit the design of improved NAMPT inhibitors as more efficient drugs against cancer[2]. Design of such inhibitors may be achieved by rational design using the Kinetic Isotope Effect tool (KIE).

 

 

Selected Publications

 

[1] Burgos E.S., NAMPT in regulated NAD biosynthesis and its pivotal role in human metabolsim. Curr Med Chem, 2011, 18, (13), 1947-1961.

 

[2] Cassera M.B., Ho M.C., Merino E.F., Burgos E.S., Rinaldo-Matthis A., Almo S.C., Schramm V.L., A high-affinity adenosine kinase from Anopheles gambiae. Biochemistry, 2011, 50, (11), 1885-1893.

 

[3] Burgos, E.S.; Ho, M.C.; Almo, S.C.; Schramm, V.L., A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT. Proc Natl Acad Sci U S A, 2009, 106, (33), 13748-13753.

 

[4] Burgos, E.S.; Schramm, V.L., Weak coupling of ATP hydrolysis to the chemical equilibrium of human nicotinamide phosphoribosyltransferase. Biochemistry, 2008, 47, (42), 11086-11096.

 

[5] Stern, A.L.; Burgos, E.; Salmon, L.; Cazzulo, J.J., Ribose 5-phosphate isomerase type B from Trypanosoma cruzi: kinetic properties and site-directed mutagenesis reveal information about the reaction mechanism. Biochem J, 2007, 401, (1), 279-285.

 

[6] Roos, A.K.; Burgos, E.; Ericsson, D.J.; Salmon, L.; Mowbray, S.L., Competitive inhibitors of Mycobacterium tuberculosis ribose-5-phosphate isomerase B reveal new information about the reaction mechanism. J Biol Chem, 2005, 280, (8), 6416-6422.

 

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Contact

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room 301
Bronx, NY 10461

Tel: 718.430.2777
Fax: 718.430.8565
emmanuel.burgos@einstein.yu.edu

 
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