** POST DOCTORAL POSITION IN STRUCTURAL ENZYMOLOGY AND INHIBITOR DESIGN ** A post doctoral position is available immediately in the laboratories of Vern Schramm and Steve Almo in the Department of Biochemistry at the Albert Einstein College of Medicine. This program utilizes high resolution crystallographic analysis and kinetic isotope effects to define the fundamental chemical and physical determinants of enzymatic rate enhancement, and to design highly specific transition state analogs with affinities in the nM and pM ranges. These efforts are focused on the enzymes involved in nucleotide metabolism in bacterial, fungal and mammalian organisms and have produced a number of therapeutic leads that are currently being utilized in animal studies and clinical trials for malaria, T cell lymphoma and autoimmunity.
The successful applicant must have extensive experience in all aspects of high resolution protein crystallography and a strong desire to complement these skills with mechanistic enzymology and state-of-the-art transition state analysis, with an overall goal of developing new therapeutic approaches. Representative publications describing this program include: Fedorov, et al. (2001) “Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. Biochemistry 40(4):853-60. Lewandowicz, et al. (2003) Over-the-barrier transition state analogues and crystal structure with Mycobacterium tuberculosis purine nucleoside phosphorylase. Biochemistry 42(20):6057-66. Singh, et al. (2004) Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A. Biochemistry 43(1):9-18. Kim, et al. (2006) Structural and kinetic characterization of Escherichia coli TadA, the wobble-specific tRNA deaminase. Biochemistry 45(20):6407-16. Singh, et al. (2006) Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae. Biochemistry 45(43):12929-41. Murkin, et al. (2007) Neighboring group participation in the transition state of human purine nucleoside phosphorylase. Biochemistry 46(17):5038-49. Albert Einstein provides an outstanding scientific environment that includes considerable strengths in microbiology, immunology, cancer biology, mechanistic enzymology, biophysics, computational biology and structural genomics. Close proximity to the National Synchrotron Light Source at Brookhaven National Laboratory ensures extensive and sustained access to several bending magnet and insertion device beamlines. This position affords the successful applicant with the opportunity to exploit their expertise in structural biology within the context of a strong biological program focused on inhibitor and therapeutic development. Interested applicants should provide a CV and arrange for three letter of reference to be sent directly to [EMAIL PROTECTED]
