The Zhou lab focuses on the elucidation of the structure, dynamics, and function of protein-protein and protein-ligand interactions and their roles in various cellular processes. Our current efforts are directed toward enzymes and protein complexes involved in bacterial membrane biosynthesis, co-transcriptional regulation, and translesion DNA synthesis. In order to achieve these goals, the Zhou lab integrates a variety of biochemical and biophysical tools, including NMR, X-ray crystallography, enzymology, and others. The lab has also played a major role in development and application of innovative NMR technologies, including automated resonance assignment and structural analysis tools and high-resolution, high-dimensional spectral reconstruction techniques.
Generalized Reconstruction of n-D NMR Spectra from Multiple Projections: Application to the 5-D HACACONH Spectrum of Protein G B1 Domain. Coggins BE, Venters RA, Zhou P. J Am Chem Soc 126, 1000-1001 (2004).
Filtered Backprojection for the Reconstruction of a High-Resolution (4,2)D CH3-NH NOESY Spectrum on a 29 kDa Protein. Coggins BE, Venters RA and Zhou P. J Am Chem Soc 127, 11562-11563 (2005).
Fourier Transforms of Radially-Sampled NMR Data. Coggins BE and Zhou P. J Magn Reson 182, 84-95 (2006).
High resolution 4-D spectroscopy with sparse concentric shell sampling and FFT-CLEAN. Coggins BE and Zhou P. J Biomol NMR 42, 225–239 (2008).
Fast Acquisition of High Resolution 4-D Amide-Amide NOESY with Diagonal Suppression, Sparse Sampling and FFT-CLEAN. Werner-Allen JW, Coggin BE and Zhou P. J Magn Reson204,:173-178 (2010).
Sparsely-sampled high-resolution 4-D experiments for efficient backbone resonance assignment of disordered proteins. Wen J, Wu J, and Zhou P. J Magn Reson 209, 94-100 (2011).
Efficient acquisition of high-resolution 4-D diagonal-suppressed methyl-methyl NOESY for large proteins. Wen J, Zhou P, Wu J. J Magn Reson. 2012 May;218:128-32.
measurements of reconstruction fidelity of sparsely sampled magnetic
resonance spectra. Wu Q, Coggins BE, Zhou P. Nature Communications
2016; 7: 12281.
Structure of the LpxC deacetylase with a bound substrate-analog inhibitor. Coggins BE, Li X, McClerren AL, Hindsgaul O, Raetz CRH, Zhou P.Nat Struct Biol 10, 645-651 (2003).
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: time-dependent inhibition and specificity in ligand binding. Barb A, Jiang L, Raetz CRH and Zhou P. Proc Natl Acad Sci USA 104, 18433-18438 (2007).
Species-specific and inhibitor-dependent conformations of LpxC-Implications for antibiotic design. Lee CJ, Liang X, Chen X, Zeng D, Joo SH, Chung HS, Barb AW, Swanson SM, Nicholas RA, Li Y, Toone EJ, Raetz CRH, Zhou P. Chemistry and Biology 18: 38-47 (2011).
Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis. Nguyen BD, Cunningham D, Liang X, Chen X, Toone EJ, Raetz CR, Zhou P, Valdivia RH. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10284-9.
Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis. Zeng D, Zhao J, Chung HS, Guan Z, Raetz CR, Zhou P. J Biol Chem. 2013; 288: 5475-86.
Structural Basis of the Promiscuous Inhibitor Susceptibility of E. coli LpxC. Lee C-J, Liang X, Gopalaswamy R, Najeeb J, Ark, ED, Toone EJ, and Zhou P. ACS Chem. Biol. 2014 Jan 17;9(1):237-46.
Drug design from the cryptic inhibitor envelope. Lee C-J, Liang X, Wu Q, Najeeb J, Zhao J, Gopalaswamy R, Titecat M, Sebbane F, Lemaitre N, Toone EJ, Zhou P. Nature Communications 2016; 7: 10638.
Treatment of Severe Gram-Negative Bacterial Infections
by a New Class of Antibiotics Targeting LpxC. Lemaître N, Liang X,
Najeeb J, Lee CJ, Titecat M, Leteurtre E, Simonet M, Toone EJ, Zhou P*,
Sebbane F*. MBio.
2017 Jul 25;8(4). pii: e00674-17.
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase h. Bomar MG, Pai M, Tzeng S, Li S and Zhou P. EMBO reports 8, 247-251 (2007).
Unconventional Ubiquitin Recognition by the Ubiquitin-Binding Motif within the Y Family DNA Polymerases i and Rev1. Bomar MG, D’Souza S, Bienko M, Dikic I, Walker GC, and Zhou P. Molecular Cell 37, 408-417 (2010).
Multifaceted recognition of vertebrate Rev1 by translesion polymerases zeta and kappa. Wojtaszek J, Liu J, D'Souza S, Wang S, Xue Y, Walker GC, Zhou P. J Biol Chem. 2012 July 27; 287 (31): 26400-8.
Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric Pol zeta and Pol kappa. Wojtaszek J, Lee CJ, D'Souza S, Minesinger B, Kim H, D'Andrea AD, Walker GC, and Zhou P. J Biol Chem. 2012; 287(40):33836-46.
recognition by FAAP20 expands the complex interface
beyond the canonical UBZ domain. Wojtaszek JL, Wang S, Kim H, Wu Q,
D'Andrea AD, Zhou P. Nucleic Acids Research,
2014; 42: 13997-4005.