Structures of Glycinamide Ribonucleotide Transformylase (PurN) from Mycobacterium tuberculosis Reveal a Novel Dimer with Relevance to Drug Discovery

Journal of Molecular Biology

Volumn 389, Issue 4, 2009, Pages 722-733

  Zhang, Zhening ^a   Caradoc Davies, Tom T ^a   Dickson, James M ^a   Baker, Edward N ^a   Squire, Christopher J ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

glycinamide ribonucleotide transformylase; Mycobacterium tuberculosis; purine biosynthesis; PurN; X ray crystallography

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID; DIMER; HALIDE; IODIDE ION; MAGNESIUM; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE;

ARTICLE; BINDING SITE; DIMERIZATION; ENZYME ACTIVE SITE; ENZYME ANALYSIS; ENZYME STRUCTURE; ESCHERICHIA COLI; MOLECULAR MECHANICS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FOLDING;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; MYCOBACTERIUM TUBERCULOSIS;

EID: 65849218106     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.04.044     Document Type: Article

References (32)

1. Aimi J., Qiu H., Williams J., Zalkin H., and Dixon J.E. De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. coli. Nucleic Acids Res. 19 (1990) 6665-6672
2. Boldt R., and Zrenner R. Purine and pyrimidine biosynthesis in higher plants. Physiol. Planatarum 117 (2003) 297-304
3. McGuire J.J. Anticancer antifolates: current status and future directions. Curr. Pharm. Des. 9 (2003) 2593-2613
4. Gooljarsingh L.T., Ramcharan J., Gilroy S., and Benkovic S.J. Localization of GAR transformylase in Escherichia coli and mammalian cells. Proc. Natl Acad. Sci. USA 98 (2001) 6565-6570
5. Almassy R.J., Janson C.A., Kan C., and Hostomska Z. Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase. Proc. Natl Acad. Sci. USA 89 (1992) 6114-6118
6. Boger D.L., Haynes N.-E., Kitos P.A., Warren M.S., Ramcharan J., Marolewski A.E., and Benkovic S.J. 10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF): a potent inhibitor of glycinamide ribonucleotide transformylase. Bioorg. Med. Chem. 5 (1997) 1817-1830
7. Sassetti C.M., Boyd D.H., and Rubin E.J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48 (2003) 77-84
8. Chen P., Schulze-Gahmen U., Stura E.A., Inglese J., Johnson D.L., Marolewski A., et al. Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy. J. Mol. Biol. 227 (1992) 283-292
9. Zhang Y., Desharnais J., Greasley S.E., Beardsley G.P., Boger D.L., and Wilson I.A. Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR. Biochemistry 41 (2002) 14206-14215
10. Daubner S.C., Schrimsher J.L., Schendel F.J., Young M., Henikoff S., Patterson D., et al. A multifunctional protein possessing glycinamide ribonucleotide synthetase, glycinamide ribonucleotide transformylase, and aminoimidazole ribonucleotide synthetase activities in de novo purine biosynthesis. Biochemistry 24 (1985) 7059-7062
11. Shim J.H., and Benkovic S.J. Evaluation of the kinetic mechanism of Escherichia coli glycinamide ribonucleotide transformylase. Biochemistry 37 (1998) 8776-8782
12. Klein C., Chen P., Arevalo J.H., Stura E.A., Marolewski A., Warren M.S., et al. Towards structure-based drug design: crystal structure of a multisubstrate adduct complex of glycinamide ribonucleotide transformylase at 1.96 resolution. J. Mol. Biol. 249 (1995) 153-175
13. Greasley S.E., Yamashita M.M., Cai H., Benkovic S.J., Boger D.L., and Wilson I.A. New insights into inhibitor design from the crystal structure and NMR studies of Escherichia coli GAR transformylase in complex with beta-GAR and 10-formyl-5,8,10-trideazafolic acid. Biochemistry 38 (1999) 16783-16793
14. Greasley S.E., Marsilje T.H., Cai H., Baker S., Benkovic S.J., Boger D.L., and Wilson I.A. Unexpected formation of an epoxide-derived multisubstrate adduct inhibitor on the active site of GAR transformylase. Biochemistry 40 (2001) 13538-13547
15. Zhang Y., Desharnais J., Marsilje T.H., Li C., Hedrick M.P., Gooljarsingh L.T., et al. Rational design, synthesis, evaluation and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,9-tetrahydrofolic acid. Biochemistry 42 (2003) 6043-6056
16. Krissinel E., and Henrick K. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr. D 60 (2004) 2256-2268
17. Krissinel E., and Henrick K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372 (2007) 774-797
18. Mullen C.A., and Jennings P.A. Glycinamide ribonucleotide transformylase undergoes pH-dependent dimerization. J. Mol. Biol. 262 (1996) 746-755
19. Li C., Kappock T.J., Stubbe J., Weaver T.M., and Ealick S.E. X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 Å resolution. Structure 7 (1999) 1155-1166
20. Su Y., Yamashita M.M., Greasley S.E., Mullen C.A., Shim J.H., Jennings P.A., et al. A pH-dependent stabilization of an active site loop observed from low and high pH crystal structures of mutant monomeric glycinamide ribonucleotide transformylase at 1.8 to 1.9 Å. J. Mol. Biol. 281 (1998) 485-499
21. Marolewski A.E., Mattia K.M., Warren M.S., and Benkovic S.J. Formyl phosphate: a proposed intermediate in the reaction catalyzed by Escherichia coli PurT GAR transformylase. Biochemistry 36 (1997) 6709-6716
22. Thoden J.B., Firestine S., Nixon A., Benkovic S.J., and Holden H.M. Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase. Biochemistry 39 (2000) 8791-8802
23. Thoden J.B., Firestine S.M., Benkovic S.J., and Holden H.M. PurT-encoded glycinamide ribonucleotide transformylase. Accommodation of adenosine nucleotide analogs within the active site. J. Biol. Chem. 277 (2002) 23898-23908
24. Studier F.W. Protein production by auto-induction in high density shaking cultures. Protein Expr. Purif. 41 (2005) 207-234
25. Page R., Grzechnik S.K., Canaves J.M., Spraggon G., Kreusch A., Kuhn P., Stevens R.C., and Lesley S.A. Shotgun crystallization strategy for structural genomics: an optimized two-tiered crystallization screen against the Thermotoga maritima proteome. Acta Crystallogr. D 59 (2003) 1028-1037
26. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50 (1994) 760-763
27. Long F., Vagin A.A., Young P., and Murshudov G.N. BALBES: a molecular-replacement pipeline. Acta Crystallogr. D 64 (2008) 125-132
28. Emsley P., and Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60 (2004) 2126-2132
29. Murshudov G.N., Vagin A.A., and Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53 (1997) 240-255
30. Davis I.W., Leaver-Fay A., Chen V.B., Block J.N., Kapral G.J., Wang X., et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35 (2007) W375-W383
31. Schuttelkopf A.W., and van Aalten D.M.F. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D 60 (2004) 1355-1363
32. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., et al. The Protein Data Bank. Nucleic Acids Res. 28 (2000) 235-242