X-ray crystallography of macromolecules from infectious pathogens
We seek to understand the molecular basis of how viruses interact with the host cell and manipulate key cellular processes to aid their replication. Viral-host complexes play an integral role in the biology of the virus and range from binary protein-protein and protein-nucleic acid complexes to much larger multi-component complexes. Defining the biochemical and structural basis of these interactions offers the potential to improve the current therapeutics, develop new intervention strategies, and understand the mechanism of emergent drug resistance. To decipher the molecular basis of these interactions at the atomic resolution we use a multidisciplinary approach of diverse methodologies including virology, biochemical, biophysical, and structural biology by X-ray crystallography.
Alian A, Griner SL, Chiang V, Tsiang M, Jones G, Birkus G, Geleziunas R, Leavitt AD, and Stroud RM. Catalytically-active complex of HIV-1 integrase with a viral DNA substrate binds anti-integrase drugs. 2009, PNAS, 106: 8192-8197.
Alian A, Degiovanni A, Griner SL, Finer-Moore JS, and Stroud RM. Crystal structure of an RluF-RNA complex: a base-pair rearrangement is the key to selectivity of RluF for U2604 of the ribosome. 2009, JMB, 388: 785-800.
Alian A, Lee TT, Griner SL, Stroud RM, and Finer-Moore J. Structure of a TrmA-RNA complex: A consensus RNA fold contributes to substrate selectivity and catalysis in m5U methyltransferases. 2008, PNAS, 105: 6876-6881.
He X, Alian A, and Ortiz de Montellano PR. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. 2007, Bioorg Med Chem., 15: 6649-6658
Verras A, Alian A, and Ortiz de Montellano PR. Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450(cam) by an L244A mutation. 2006, Protein Eng Des Sel., 19: 491-496. (Cover figure)