Yousif Shamoo

Professor of Biochemistry and Cell Biology

My lab uses structural biology to investigate a wide range of areas including:
(1) Molecular architecture of DNA replication and cancer. DNA replication is important in cancer biology because its regulation plays a central role in cell proliferation and because DNA replication errors can give rise to certain forms of cancer. Replication in Archae is similar to and an excellent model for replication in humans. We are studying the functional architecture of the Archaebacteria Thermococcus kadakarensis replisome using x-ray crystallography to identify how DNA polymerases interact with cognate accessory proteins.
(2) Defining evolutionary trajectories: Molecular adaptation to stresses such as antibiotics and temperature. Using in vivo molecular evolution we are studying how an organism mutates an essential gene as a response to environmental change. We focus on two key attributes of molecular evolution; firstly, the characteristics of bacterial populations as they adapt to environmental extremes such as temperature and antibiotics, and secondly, the physicochemical properties of the proteins generated from these selections. The experiments follow populations of mutant bacteria as they compete for survival, and use x-ray crystallography to examine the atomic basis for adaptation.

Publications

Walkiewicz, K., Davlieva, M., Wu, G. and Shamoo, Y. Crystal structure of Bacteroides thetaiotaomicron TetX2, a tetracycline degrading monooxygenase at 2.8 Å resolution.  Proteins: Struc. Func. Bioinform, 79: 2335-2340. PMID 21590745

Peña, M., Van Italie, E., Bennett, M.R., and Shamoo, Y. "Evolution of a single gene highlights the complexity underlying molecular descriptions of fitness." CHAOS 20:026107 (2010). PMID:20590336

Peña, M., Davlieva, M. Bennett, M.R., Olson, J.S. and Shamoo, Y. "Evolutionary fates within a microbial population highlight an essential role for reversible and irreversible protein folding during natural selection." Molecular Systems Biology 6:387 (2010). PMID 20631681

Davlieva M, Zhang W, Arias CA, Shamoo Y. Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci.  Antimicrob Agents Chemother., 57(1) 2012: 289-96

Mishra NN, Bayer AS, Tran TT, Shamoo Y, Mileykovskaya E, Dowhan W, Guan Z, Arias CA. Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.  PLoS One, 7(8) 2012: e43958

Tran TT, Panesso D, Gao H, Roh JH, Munita JM, Reyes J, Diaz L, Lobos EA, Shamoo Y, Mishra NN, Bayer AS, Murray BE, Weinstock GM, Arias CA. Whole-Genome Analysis of a Daptomycin-Susceptible Enterococcus faecium Strain and Its Daptomycin-Resistant Variant Arising during Therapy.  Antimicrob Agents Chemother., 57(1) 2012: 261-8

Arias, C.A., McGrath, D., Qin, X.,Mojica M.F., Miller C., Diaz S. L., Tran, T.T., Rincon, S., Barbu, E.M., Reyes, J.C., Panesso, D., Lobos, E., Sodergren, E., Pasqualini, R., Arap, W., Quinn, J.P., Shamoo, Y., Murray, B.E., and Weinstock, G. Whole-Genome and Cell Envelope Analysis of Daptomycin- Susceptible Enterococcus faecalis and Its Resistant Derivative that Arose During Therapy.  New Engl. J. Med., 362 2011: 892-900. PMID 21899450

Walkiewicz K., Lau K. and Shamoo Y. Biophysical basis for TetX mediated antibiotic resistance.   2010

Davilieva, M. and Shamoo, Y. Crystal structure of a trimeric archaeal adenylate kinase from the mesophile Methanococcus maripaludis with an unusually broad functional range and thermal stability.  Proteins, 78 2010: 357-364

Miller C. and Shamoo Y. Experimental Evolution of Daptomycin Resistance in Enterococcus Faecalis.   2010

Miller, C., Davilieva, M., Wilson, C., White, K., Counago, R., Wu, G., Myers, J.C., Wittung-Stafshede, P., and Shamoo, Y. Experimental evolution of adenylate kinase reveals contrasting strategies towards protein thermostability.  Biophys. J, 99 2010: 887-896 PMID: 20682267

Peña M., Davlieva M., Bennett M.R., Olson J.S. and Shamoo Y. Protein folding dynamics and function determine evolutionary fates in a microbial population.   2010

Davlieva M., Doneske J., Michnicka M., Nikonowicz E. and Shamoo Y. Structural studies of an RNA aptamer with high affinity for the B. anthracis ribosomal protein S8.   2010

Guelker, M., Stagg, L., Wittung-Stafshede, P., and Shamoo, Y. Pseudo symmetry, high copy number and twinning complicate the structure determination of flavodoxin from Desulfovibrio desulfuricans (ATCC 29577).  Acta Cryst D Biol Crystallogr, D65 2009: 513-522

Davlieva, M. and Shamoo, Y. Structure and biochemical characterization of an adenylate kinase originating from the psychrophilic organism Marinibacillus marinus .  Acta Cryst F Struc Biol Cryst Commun, 65 2009: 751-756

Couñago, R., Wilson, C.J., Peña, M.I., Wittung-Stafshede, P., and Shamoo, Y. An adaptive mutation in adenylate kinase that increases organismal fitness is linked to stability-activity trade-offs.  Prot. Eng. Des. Sel., 21 2008: 19-27

Woodward, A.W., Ratzel, S.E., Woodward, E.E., Shamoo, Y., and Bartel, B. Mutation of E1-CONJUGATING ENZYME-RELATED1 decreases RELATED TO UBIQUITIN conjugation and alters auxin response and development.  Plant Physiology, 144 2007: 976-987

Counago, R., Chen, S. and Shamoo, Y. In vivo evolution reveals biophysical origins of organismal fitness.  Molecular Cell, 22 2006: 441-446

Brock, D.A., van Egmond, W.N., Shamoo. Y., Hatton, R.D., and Gomer, R.H. A 60-kilodalton protein component of the counting factor regulates group size in Dictyostelium discoideum.  Eularyotic Cell, 5 2006: 1532-1538

Maximciuc, A., Putkey, J.A., Shamoo, Y., and Mackenzie, K.R. Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible binding mode.  Structure, 14 2006: 1547-1556

Sun, S., Geng, L., and Shamoo, Y. Fusion of bacteriophage RB69 DNA polymerase and single-stranded DNA binding protein leads to increased processivity.  Prot. Struc. Func. and Bioinform., 65 2006: 231-238

Morozova, N., Aller, J.A., Myers, J., and Shamoo, Y. Protein-RNA interactions: Exploring binding patterns with a three-dimensional superposition analysis of high resolution structures.  Bioinformatics, 22 2006: 2746-2752

Counago, R., and Shamoo, Y. Gene replacement of adenylate kinase in the gram-positive thermophile Geobacillus stearothermophilus disrupts adenine nucleotide homeostasis and reduces cell viability.  Extremophiles, 9 2005: 135-144

Myers, J., and Shamoo, Y. Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA Recognition Motif (RRM).  J. Mol. Biol., 342 2004: 743-756

Bruning, J.B., and Shamoo, Y. Structural and thermodynamic analysis of human PCNA bound to peptides derived from DNA polymerase-delta p66-subunit and flap endonuclease-1 (FEN1) proteins.  Structure 2004In Press

Sun, S., and Shamoo, Y. Biochemical characterization of interactions between DNA polymerase and single-stranded DNA binding protein in bacteriophage RB69.  J. Biol. Chem., 278 2003: 3876-3881

Shamoo, Y. Structural insights into BRCA2 function.  Curr. Op. Struc. Biol., 13 2003: 206-211

Myers, J.G., Moore, S.A., and Shamoo, Y. Structure-based incorporation of 6-MI into the human telomeric repeat DNA as a probe for UP1 binding and destabilization of G-tetrad structures.  J. Biol. Chem., 278 2003: 42300-42306

Allers, J., and Shamoo, Y. Structure-based analysis of protein-RNA interactions using the program ENTANGLE.  J. Mol. Biol., 311 2001: 76-86

Shamoo, Y. Single-stranded DNA Binding Proteins.  in Encyclopedia of Life Sciences 2000

Shamoo, Y., and Steitz, T.A. Building a Replisome Structure from Interacting Pieces: Structures of a Sliding Clamp Complexed with an Interaction Peptide from DNA Polymerase, and a DNA Polymerase Editing Complex.  Cell, 99 1999: 155-169

Rice, L.M., Shamoo, Y., and Brunger, A.T Phase Improvement by Multi-start Simulated Annealing Refinement and Structure Factor Averaging.  J. Appl. Cryst., 31 1998: 798-805

Walkiewicz K, Benitez Cardenas AS, Sun C, Bacorn C, Saxer G, Shamoo Y. Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance.  Proc Natl Acad Sci U S A., 109(52) 2012 Dec 26: 21408-13