Department of Biology
18 Mudd Hall
Department of Biology
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218-2685
Office 410 516-7776
Lab 410 516-7776
Departmental fax 410 516-5213
Washington UniversityBiochemistry and Enzymology, Synthesis of Nucleic Acid Derivatives, Proteomics
We are currently studying the Nudix hydrolase family of enzymes. This is a large, widely distributed class of proteins that we have discovered having the common signature sequence:
GX6EX7REUXEEXU (U= Ile, Leu, or Val)
At present, over 600 members of the family have been identified in more than 200 species by BLAST searches of the data banks, and this number is increasing daily. We are system-atically cloning selected members of the family, expressing them in E.coli, purifying the proteins and attempting to identify their function. This seemingly difficult task has been made practicable by our discovery that the common feature of the substrates of these enzymes is that they are all Nucleoside diphosphates linked to some other moiety, x, hence the acronym, Nudix. These enzymes can be thought of as surveillance proteins, because their substrates are either potentially toxic to the cell, are signaling molecules, or intermediates whose concentrations require modulation durrng cellular metabolism.
Xu W, Dunn CA, O'handley SF, Smith DL, Bessman MJ 2006. Three New Nudix Hydrolases from Escherichia coli. J Biol Chem. 281(32):22794-8.
Edelstein PH, Hu B, Shinzato T, Edelstein MA, Xu W, Bessman MJ 2005. Legionella pneumophila NudA Is a Nudix hydrolase and virulence factor. Infect Immun. 73(10):6567-76.
Urick T, I-Chang C, Arena E, Xu W, Bessman MJ, Ruffolo CG 2005. The pnhA gene of Pasteurella multocida encodes a dinucleoside oligophosphate pyrophosphatase member of the Nudix hydrolase superfamily. J Bacteriol. 2005 Aug;187(16):5809-17
Ranatunga, W., Hill, E.E., Mooster,J. L., Holbrook, E. L., Schulze-Gahmen, U., Xu, W-L., Bessman, M. J., Brenner, S. E., Holbrook, S. R. 2004. Structural Studies of the Nudix Hydrolase DR1025. From Deinococcus radiodurans and its Ligand Complexes. J. Mol. Biol. 339, 103-116.
Xu, W.-L., Dunn, C.A., Jones, C. R., D'Souza, G., Bessman, M. J. 2004. The 26 Nudix Hydrolases of Bacillus cereus, a Close Relative of Bacillus anthracis. J.Biol. Chem. 279, 24861-24865.
Xu, W.-L., Shen, J-Y. , Dunn, C. A. , Bessman , M. J. 2003. A New Subfamily of the Nudix Hydrolase Superfamily Active on 5-methyl-UTP (riboTTP) and UTP. J. Biol. Chem. 278, 37492-37496.
Kang, L.-W., Gabelli, S. B., Bianchet, M. A., Xu, W-L., Bessman, M. J. and Amzel,L. M. 2003. Structure of a Coenzyme A Pyrophosphatase from Deinococcus radiodurans : A Member of the Nudix Family. J. Bacteriol. 185, 4110-4118.
Perraud, A.-L., Shen, B., Dunn, C. A., Rippe, K., Smith, M. K., Bessman, M. J., Stoddard, B. L., and Scharenberg, A. M. 2003. NUDT9, a Member of the Nudix Hydrolase Family, Is an Evolutionarily Conserved Mitochondrial ADP-ribose Pyrophosphatase. J. Biol. Chem. 278, 1794-1801.
Xu, W.-L., Gauss, P., Shen, J.-Y., Dunn, C. A. and Bessman, M. J. 2002. The Gene, e.1(nudE.1), of T4 Bacteriophage Designates a New Member of the Nudix Hydrolase Superfamily Active on Flavin Adenine Dinucleotide , Adenosine (5')triphospho(5')adenosine, and ADP-ribose. J. Biol. Chem. 174, 23181-23185.
Bessman, M. J., Walsh, J. D., Dunn, C. A., Swaminathan, J., Weldon, J.E. and Shen, J. 2001. The Gene ygdP, Associated with the Invasiveness of Escherichia coli K1, Designates a Nudix Huydrolase, Orf176, Active on Adenosine (5')-Pentaphospho-(5')-Adenosine (Ap5A). J. Biol. Chem. 276, 37834-37838.
S.B. Gabelli, M. A. Bianchet, M. J. Bessman and L. M. Amzel, 2001. The Structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family, Nature Structure 98, 467-472.
A. L. Perraud, A. Fleig, C.A. Dunn, L. A. Bagley, P. Launay, C. Schmitz. A. J. Stokes, Q. Zhu, M. J. Bessman, J.-P. Kinet and A. M. Scharenberg 2001. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411, 595-599.
W.-L. Xu, J.-Y. Shen, C. A. Dunn, S. Desai and M. J. Bessman, 2001. The Nudix Hydrolases of Deioncoccus radiodurans. Mol. Micro, 39, 286-290.
S. F. O'Handley, C. A. Dunn and M. J. Bessman 2001. Orf135 from Escherichia coli is a Nudix Hydrolase Specific for CTP, dCTP, and 5-Methyl-dCPT. J. Biol. Chem. 276, 5421-5426.
W.-L., Xu, C. A. Dunn and M. J. Bessman, 2000. Cloning and Characterization of the NADH Pyrophosphatase from Caenorhabditis elegans and Saccharomyces cerevisiae, Members of a Nudix Hydrolase Subfamily. Biochem., Biophsy. Res. Communs. 273, 753-758.