Department of Biochemistry

Duke University Medical Center

News

	World Health Day – 7 April 2011 Antimicrobial resistance: no action today, no cure tomorrow    (Read more)
	The March, 2011  issue of The Economist published a special report on antibiotic resistance: The spread of superbugs. (Read more)
	Prof. Pei Zhou spoke at the Cambridge Healthtech Institute's (CHI) PEPTALK conference (Jan 10-14, 2011) at San Diego, CA on using Solubility-enhancement tags (SETs) for solution NMR studies of challenging proteins.
	Congratulations to Jon Werner-Allen, who has been invited for an oral presentation at the Keystone Symposium: Frontiers of NMR in Biology, Jan 8 - Jan 13, 2011, Big Sky Resort in Big Sky, Montana.
	Congratulations to Su Wang for winning the Graduate Student Poster Award at the 2010 Duke Biochemistry Departmental Retreat at the Wrightsville Beach, NC (09/17/2010-09/19/2010).

Research Interests
Protein-protein interactions play a pivotal role in the regulation of various cellular processes. The formation of higher order protein complexes is frequently accompanied by extensive structural remodeling of the individual components, varying from domain re-orientation to induced folding of unstructured elements. Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for macromolecular structure determination in solution. It has the unique advantage of being capable of elucidating the dynamic behavior of proteins during the process of recognition. Recent advances in NMR techniques have enabled the study of significantly larger proteins and protein complexes. These innovations have also led to faster and more accurate structure determination. My research interests focus on the exploration of molecular recognition and conformational variability of protein complexes in crucial biomedical processes using state-of-the-art NMR techniques. (More)

Recent Publications

	--------- 2011 ---------
	43. 1H, 13C and 15N backbone and side-chain resonance assignments of Drosophila melanogaster Ssu72. Werner-Allen JW, Zhou P. Biomol NMR Assign. 2011 Jul 6. [Epub ahead of print]
	42. Protein Side-Chain Resonance Assignment and NOE Assignment Using RDC-Defined Backbones without TOCSY Data. Zeng J, Zhou P and Donald BR. J Biomol NMR. 2011 Jun 25. [Epub ahead of print]
	41. 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.
	40. A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers. Martin JW, Yam AK, Bailey-Kellogg C, Zhou P and Donald BR. Protein Sci 2011; 20: 970-85.
	39. 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).
	38. Cis proline-mediated pSer5-dephosphorylation by the RNA polymerase II CTD phosphatase Ssu72. Werner-Allen JW, Lee CJ, Liu P, Nicely NI, Wang S, Greenleaf AL, Zhou P. Journal of Biological Chemistry 286, 5717-5826 (2011). (PDB: 3P3Y)
	37. Syntheses, structures and antibiotic acitivities of LpxC inhibitors based on the diacetylene scaffold. Liang X, Lee CJ, Chen X, Chung HS, Zeng D, Raetz CRH, Li Y, Zhou P, Toone EJ. Bioorganic & Medicinal Chemistry 19: 852-60 (2011). (PDB: 3PS1, 3PS2, 3PS3)
	36. 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: 1-10 (2011). (PDB: 3P3C, 3P3E, 3P3G)

--------- 2010 ---------

	35. HDAC6 and Ubp-M BUZ Domains Recognize Specific C-Terminal Sequences of Proteins. Hard RL, Liu J, Shen J, Zhou P, Pei D. Biochemistry  49:10737-46 (2010).
	34. The unusual UBZ domain of Saccharomyces cerevisiae polymerase eta. Woodruff RV, Bomar MG, D'Souza S, Zhou P, Walker GC. DNA Repair 9: 1130-41 (2010).
	33. Radial Sampling for Fast NMR: Concepts and Practices Over Three Decades. Coggins BE, Venters RA, and Zhou P. Progress in Nuclear Magnetic Resonance Spectroscopy 57: 381-419 (2010). Review.
	32. 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 Reson 204,:173-178 (2010) (PDF).
	31. 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) (PDF).
	30. Assignment of 1H, 13C and 15N backbone resonances of Escherichia coli LpxC bound to L-161,240. Barb AW, Jiang L, Raetz CR and Zhou P. Biomol NMR Assign (PMID: 19941092) (PDF).
	29. Overcoming the Solubility Limit with Solubility-Enhancement Tags: Successful Applications in Biomolecular NMR Studies. Zhou P and Wagner G. J Biomolecular NMR 46: 23-31 (2010) (Review).

------ 2009 and previous years ------

28. High-resolution protein structure determination starting with a global fold calculated from exact solutions to the RDC equations. Zeng J, Boyles J, Tripathy  C, Wang L, Yan A, Zhou P and Donald BR.  J Biomolecular NMR 45: 265-81 (2009). (PDF).

27. Uridine-based inhibitors as new leads for antibiotics targeting E. coli LpxC. Barb AW, Leavy TM , Robins L, Guan Z , Six D, Zhou P, Bertozzi C and Raetz CRH. Biochemistry 48, 3068-77 (2009). (PDF)

26. A Hausdorff-based NOE assignment algorithm using protein backbone determined from residual dipolar couplings and rotamer patterns. Zeng JM, Tripathy C, Zhou P and Donald BR. Comput Syst Bioinformatics Conf 2008:169-181 (2008). (PDF) (Supplementary Information)

25. Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis. Barb AW and Zhou P. Curr Pharm Biotechnol 9, 9-15 (2008). (Review).

24. 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) (PDF).

23. 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). (PDF)

22. The ADAM10 prodomain is a specific inhibitor of ADAM10 proteolytic activity and inhibits cellular shedding events. Moss ML, Bomar M, Liu Q, Sage H, Dempsey P, Lenhart PM, Gillispie PA, Stoeck A, Wildeboer D, Bartsch JW, Palmisano R, Zhou P. J Biol Chem 282, 35712-35721 (2007). (PDF) 

21. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Brower-Toland B, Findley SD, Jiang L, Liu L, Yin H, Dus M, Zhou P, Elgin SCR and Lin H. Genes & Development 21, 2300-2311 (2007). (Cover Image)

20. The low affinity IgE receptor (CD23) is cleaved by the metalloproteinase ADAM10. Lemieux GA, Blumenkron F, Yeung N, Zhou P, Williams J, Grammer AC, Petrovich R, Lipsky PE, Moss ML, Werb Z. J Biol Chem 282, 14836-44 (2007). (PDF)  

19. Solution Structure of the Ubp-M BUZ Domain, a Highly Specific Protein Module that Recognizes the C-terminal Tail of Free Ubiquitin. Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P. J Mol Biol 370, 290-302 (2007).  (PDF)

18. Inhibition of Lipid A Biosynthesis as the Primary Mechanism of CHIR-090 Antibiotic Activity in Escherichia coli. Barb AW, McClerren AL, Snehelatha K, Reynolds CM, Zhou P, Raetz CRH. Biochemistry 46, 3793-3802 (2007).  (PDF)

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). (PDF) (Supplementary Information)

16. Sampling of the NMR time domain along concentric rings. Coggins BE and Zhou P. J Magn Reson, 184, 207-221 (2007). (PDF)

15. Fourier Transforms of Radially-Sampled NMR Data. Coggins BE and Zhou P. J Magn Reson 182, 84-95 (2006). (PDF) (Cover Image)

14. A 'just-in-time' HN(CA)CO experiment for the backbone assignment of large proteins with high sensitivity. Werner-Allen JW, Jiang L, and Zhou P. J Magn Reson 181, 177-180 (2006). (PDF) (Pulse Sequence)

13. PR-CALC: A Program for the Reconstruction of NMR Spectra from Projections. Coggins BE and Zhou P. J Biomol NMR  34, 179-95 (2006). (PDF) (Supplementary Material) 

12. Evaluating the quality of NMR structures by local density of protons. Ban YA, Rudolph J, Zhou P and Edelsbrunner H. Proteins: Structure, Function, and Bioinformatics 62, 852-864 (2006). (PDF)

11.  Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1.  Li M, Phatnani HP, Guan Z, Sage H, Greenleaf AL, and Zhou P. Proc Natl Acad Sci USA 102, 17636-17641 (2005). (PDF) (Supplementary Material)
 
10.  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). (PDF) (Supplementary Materials)

9.  (4,2)D Projection-Reconstruction Experiments for Protein Backbone Assignment:  Application to Human Carbonic Anhydrase II and Calbindin D_28K.  Venters RA,  Coggins BE, Kojetin D,  Cavanagh J and Zhou P. J Am Chem Soc 127, 8785-8795 (2005). (PDF) (Supplementary Material)

8.  Rapid assignment of protein side chain resonances using projection-reconstruction of (4,3)D HC(CCO)NH and intra-HC(C)NH experiments. Jiang L, Coggins BE and Zhou P. J Magn Reson  175, 170-176 (2005). (PDF)

7.  Refined Solution Structure of the LpxC-TU-514 Complex and pKa Analysis of an Active Site Histidine: Insights into the Mechanism and Inhibitor Design. Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CRH, and Zhou P. Biochemistry 44, 1114-1126 (2005). (PDF)

6.  Kinetic Analysis of the Zinc-Dependent Deacetylase in the Lipid A Biosynthetic Pathway. McClerren AL, Zhou P, Guan Z, Raetz CRH, and Rudolph J. Biochemistry 44, 1106-1113 (2005). (PDF)

5.  Assignment of the ¹H, ¹³C and ¹⁵N Resonances of the LpxC Deacetylase from Aquifex aeolicus in Complex with the Substrate-Analog Inhibitor TU-514. Coggins BE, Li X, Hindsgaul O, Raetz CRH, Zhou P. J Biomol NMR 28, 201-202 (2004). PubMed Abstract

4.  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). (PDF) 

3.  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). (PDF)

2.  Characteristics of the Interaction of a Synthetic Human Tristetraprolin Tandem Zinc Finger Peptide with AU-rich Element-containing RNA Substrates. Blackshear PJ, Lai WS, Kennington EA, Brewer G,  Wilson GM, Guan X and Zhou P. J Biol Chem 278,19947-19955 (2003). (PDF)

1.  PACES: Protein sequential assignment by computer-assisted exhaustive search. Coggins BE  and Zhou P. J Biomol NMR 26, 93-111 (2003). (PDF)

------ Ph.D. and Postdoctoral Research ------ 

P7. A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada. He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dotsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL. Mol Cell 20, 117-129 (2005).  (PDF)

P6.  A solubility-enhancement tag (SET) for NMR studies of poorly behaving proteins. Pei Zhou, Alexey A. Lugovskoy and Gerhard Wagner. J Biomolecular NMR 20, 11-14 (2001) (PDF)

P5.  Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45. Pei Zhou, Alexey A. Lugovskoy, John S. McCarty, Peng Li and Gerhard Wagner. Proc. Natl. Acad. Sci. USA 98, 6051-6055 (2001) (PDF)

P4.  Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis. Alexey A. Lugovskoy , Pei Zhou, James J. Chou, John S. McCarty, Peng Li and Gerhard Wagner. Cell 99, 747-755 (1999) (PDF)

P3.  Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase interaction. Pei Zhou, James J. Chou, Roberto Sanchez Olea, Junying Yuan and Gerhard Wagner. Proc. Natl. Acad. Sci. USA 96, 11265-11270 (1999) (PDF)

P2.  Solution Structure of the Core NFATC1/DNA complex. Pei Zhou, Li Jing Sun, Volker Dötsch, Gerhard Wagner and Gregory L. Verdine. Cell 92, 687-696 (1998) (PDF)

P1. Unusual Rel-like Architecture in the DNA-binding Domain of the Transcription Factor NFATc. Scot A. Wolfe, Pei Zhou, Volker Dötsch, Lin Chen, Angie You, Steffan N. Ho, Gerald R. Crabtree, Gerhard Wagner, and Gregory L. Verdine. Nature 385, 172-176 (1997). (PDF)

 Duke University

Medical Center  

Department of Biochemistry