The 2.0 Å structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor

Nature Structural Biology

Volumn 6, Issue 6, 1999, Pages 588-593

  Shi, Wuxian ^a   Li, Caroline M ^a   Tyler, Peter C ^b   Furneaux, Richard H ^b   Grubmeyer, Charles ^c   Schramm, Vern L ^a   Almo, Steven C ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b CALLAGHAN INNOVATION   (New Zealand)

^c TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; GUANOSINE PHOSPHATE; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; IMMUCILLIN GP; INOSINE PHOSPHATE; MAGNESIUM ION; PURINE DERIVATIVE; PYROPHOSPHATE; UNCLASSIFIED DRUG; IMMUCILLIN G; ION; MAGNESIUM; MAGNESIUM DERIVATIVE; MAGNESIUM PYROPHOSPHATE; NITROGEN; OXYGEN; PHOSPHATE; PYRIMIDINONE DERIVATIVE; PYRROLE DERIVATIVE; SOLVENT;

ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME INHIBITOR COMPLEX; ENZYME INHIBITOR INTERACTION; ENZYME STRUCTURE; HUMAN; HYDROGEN BOND; PRIORITY JOURNAL; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CRYSTALLIZATION; DRUG ANTAGONISM; ELECTRON; METABOLISM; MOLECULAR GENETICS; PROTEIN BINDING; PROTEIN SECONDARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CATALYTIC DOMAIN; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; DIPHOSPHATES; ELECTRONS; ENZYME INHIBITORS; HUMANS; HYDROGEN BONDING; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; IONS; MAGNESIUM; MAGNESIUM COMPOUNDS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NITROGEN; OXYGEN; PHOSPHATES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PYRIMIDINONES; PYRROLES; SOLVENTS;

EID: 0032587578     PISSN: 10728368     EISSN: None     Source Type: Journal    
DOI: 10.1038/9376     Document Type: Article

References (28)

1. Krenitsky, T.A., Papaioannou, R. & Elion, G.B. Human hypoxanthine phosphoribosyl transferase: purification, properties and specificity. J. Biol. Chem. 244, 1263-1270 (1969).
2. Ullman, B. & Carter, D. Hypoxanthine-guanine phosphoribosyl-transferase as a therapeutic target in protozoan infections. Infect. Agents Dis. 4, 29-40 (1995).
3. Musick, D.L. Structural features of the phosphoribosyltransferases and their relationship to the human deficiency disorders of purine and pyrimidine metabolism. CRC Crit. Rev. Biochem. 11, 1-34 (1981).
4. Eads, J.C., Scapin, G., Xu, Y., Grubmeyer, C. & Sacchettini, J.C. The crystal structure of human hypoxanthine-guanine phosphorifaosyl-transferase with bound GMP. Cell 78, 325-334 (1994).
5. Scapin, G., Ozturk, D.H., Grubmeyer, C. & Sacchettini, J.C. The crystal structure of the orotate phosphoribosyltransferase complexed with orotate and α-D-phosphoribosyl-1-pyrophosphate. Biochemistry 34, 10744-10754 (1995).
6. Somoza, J.R., Chin, M.S., Foda, P.J., Wang C.C. & Fletterick R.J. Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyl-transferase from the protozoan parasite Tritrichomonas foetus. Biochemistry 35, 7032-7040 (1996).
7. Schumacher, M.A., Carter, D., Roos, D.S., Ullman, B. & Brennan R.G. Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop. Nature Struct. Biol. 3, 881-887 (1996).
8. Focia, P.J., Craig, S.P. & Eakin, A.E. Approaching the transition state in the crystal structure of a phosphoribosyltransferase. Biochemistry 37, 17120-17127 (1998).
9. Krahn, J.M., Kim, J.H., Burns, M.R., Parry, R.J. Zalkin, H. & Smith, J.L. Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site. Biochemistry 36, 11061-11068 (1997).
10. Xu, Y., Eads, J., Sacchettini, J.C. & Grubmeyer, C. Kinetic mechanism of human hypoxanthine-guanine phosphoribosyltransferase: rapid phosphoribosyl transfer chemistry. Biochemistry 36, 3700-3712 (1997).
11. Li, CM., Tyler, P.C., Furneaux, R.H., Kicska, G., Xu, Y, Grubmeyer, C., Girvin, M. & Schramm, V.L. Transition-state analogues as inhibitors of human and malarial hypoxanthine-guanine phosphoribosyltransferases. Nature Struct. Biol. 6, 582-587 (1999).
12. Xu, Y. & Grubmeyer, C. Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp-137 acts as a general acid/base. Biochemistry 37, 4114-4124 (1998).
13. Tao, W., Grubmeyer, C. & Blanchard, J.S. Transition state structure of Salmonella typhimurium orotate phosphoribosyltransferase. Biochemistry 35, 14-21 (1996).
14. Horenstein, B.A. & Schramm, V.L. Correlation of the molecular electrostatic potential surface of an enigmatic transition state with novel transition state inhibitors. Biochemistry 32, 9917-9925 (1993).
15. Degano, M., Almo, S.C., Sacchettini, J.C. & Schramm, V.L. Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor. Biochemistry 37, 6277-6285 (1998).
16. +. J. Am. Chem. Soc. 119, 12069-12078 (1997).
17. Vos, S., Parry, R.J., Burns, M.R., de Jersey, J. & Martin, J.L. Structures of free and complexed forms of Escherichia coli xanthine-guanine phosphoribosyltransferase. J. Mol. Biol. 282, 875-889 (1998).
18. Jardim, A. & Ullman B. The conserved serine-tyrosine dipeptide in Leishmania donovani hypoxanthine-guanine phosphoribosyltransferase is essential for catalytic activity. J. Biol. Chem. 272, 8967-8973 (1997).
19. Hove-Jensen, B., Harlow, K.W., King, C.J. & Switzer, R.L. Phosphoribosylpyrophosphate synthetase of Escherichia coli: properties of the purified enzyme and primary structure of the prs gene. J. Biol. Chem. 267, 6765-6771 (1986).
20. Wilson, J.M., Stout, J.T., Palella, T.D., Davidson, B.L., Kelley, W.N. & Caskey, C.T. A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man. J. Clin. Invest. 77, 188-195 (1986).
21. Laskowski, R.A., MacArthur, M.W. & Thorton, J.M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283-291 (1993).
22. Otwinowski, Z. & Minor, W. Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
23. Navaza, J. AmoRe: an automated package for molecular replacement. Acta Crystallogr. A 50, 157-163 (1994).
24. Brünger, A.T. X-PLOR version 3.1. (Yale University Press, New Haven, Connecticut; 1992)
25. Jones T.A. Interactive computer program graphics: Frodo. Methods Enzymol. B 115, 157-171 (1985).
26. Johnson, G.G., Eisenberg, L.R. & Migeon, B.R. Human and mouse hypoxanthine guanine phosphoribosyl transferase: dimers and tetramers. Science 203, 174-176 (1979).
27. Kraulis, P.J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946-950 (1991).
28. Evan, S.V. SETOR: hardware lighted three dimensional solid model representation of macromolecules. J. Mol. Graphics 11, 134-138 (1993).