Catalytic mechanism and molecular recognition of E. coli UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase probed by mutagenesis

Biochemistry

Volumn 45, Issue 51, 2006, Pages 15240-15248

  Hernick, Marcy ^a   Fierke, Carol A ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEACETYLASE; GLUCOSAMINES; MOLECULAR RECOGNITION; PRODUCT BINDING AFFINITY;

AMINES; BIOSYNTHESIS; CATALYSIS; ENZYMES; ESTERS; IONIZATION; MOLECULAR DYNAMICS;

ESCHERICHIA COLI;

ACETIC ACID; BACTERIAL ENZYME; ENZYME INHIBITOR; GLUCOSAMINE DERIVATIVE; LIPID A; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE 3 O (3 HYDROXYMYRISTOYL) N ACETYLGLUCOSAMINE DEACETYLASE; URIDINE DIPHOSPHATE 3 O MYRISTOYL N ACETYLGLUCOSAMINE; URIDINE DIPHOSPHATE 3 O MYRISTOYLGLUCOSAMINE;

ARTICLE; BINDING AFFINITY; ENZYME ACTIVE SITE; ENZYME MECHANISM; ENZYME SPECIFICITY; ESCHERICHIA COLI; GRAM NEGATIVE INFECTION; HYDROLYSIS; IONIZATION; LIPOGENESIS; MOLECULAR RECOGNITION; MUTAGENESIS; NONHUMAN; PKA; PRIORITY JOURNAL; PROTON TRANSPORT; STEADY STATE;

AMIDOHYDROLASES; AMINO ACID SUBSTITUTION; BINDING SITES; CATALYTIC DOMAIN; ENZYME STABILITY; ESCHERICHIA COLI PROTEINS; MUTAGENESIS, SITE-DIRECTED; PROTEIN BINDING; THERMODYNAMICS;

NEGIBACTERIA;

EID: 33845410825     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi061405k     Document Type: Article

References (40)

1. Raetz, C. R. H., and Whitfield, C. (2002) Lipopolysaccharide endotoxins, Annu. Rev. Biochem. 71, 635-700.
2. White, R. J., Margolis, P. S., Trias, J., and Yuan, Z. Y. (2003) Targeting metalloenzymes: a strategy that works, Curr. Opin. Pharmacol. 3, 502-507.
3. Onishi, H. R., Pelak, B. A., Gerckens, L. S., Silver, L. L., Kahan, F. M., Chen, M. H., Patchett, A. A., Galloway, S. M., Hyland, S. A., Anderson, M. S., and Raetz, C. R. H. (1996) Antibacterial agents that inhibit lipid A biosynthesis, Science 274, 980-982.
4. Jackman, J. E., Raetz, C. R. H., and Fierke, C. A. (1999) UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase of Escherichia coli is a zinc metalloenzyme, Biochemistry 38, 1902-1911.
5. Hernick, M., Gennadios, H. A., Whittington, D. A., Rusche, K. M., Christianson, D. W., and Fierke, C. A. (2005) UDP-3-O-((R)-3-hydroxymyristoyl)- N-acetylglucosamine deacetylase functions through a general acid-base catalyst pair mechanism, J. Biol. Chem. 280, 16969-16978.
6. Hernick, M., and Fierke, C. A. (2005) Zinc hydrolases: The mechanisms of zinc-dependent deacetylases, Arch. Biochem. Biophys. 433, 71-84.
7. Clements, J. M., Coignard, F., Johnson, I., Chandler, S., Palan, S., Waller, A., Wijkmans, J., and Hunter, M. G. (2002) Antibacterial activities and characterization of novel inhibitors of LpxC, Antimicrob. Agents Chemother. 46, 1793-1799.
8. Pirrung, M. C., Tumey, L. N., McClerren, A. L., and Raetz, C. R. H. (2003) High-throughput catch-and-release synthesis of oxazoline hydroxatnates. Structure-activity relationships in novel inhibitors of Escherichia coli LpxC: In vitro enzyme inhibition and antibacterial properties, J. Am. Chem. Soc. 125, 1575-1586.
9. Kline, T., Andersen, N. H., Harwood, E. A., Bowman, J., Malanda, A., Endsley, S., Erwin, A. L., Doyle, M., Fong, S., Harris, A. L., Mendelsohn, B., Mdluli, K., Raetz, C. R. H., Stover, C. K., Witte, P. R., Yabannavar, A., and Zhu, S. G. (2002) Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC, J. Med. Chem. 45, 3112-3129.
10. Pirrung, M. C., Tumey, L. N., Raetz, C. R. H., Jackman, J. E., Snehalatha, K., McClerren, A. L., Fierke, C. A., Gantt, S. L., and Rusche, K. M. (2002) Inhibition of the antibacterial target UDP-(3-O-acyl)-N- acetylglucosamine deacetylase (LpxC): Isoxazoline zinc amidase inhibitors bearing diverse metal binding groups, J. Med. Chem. 45, 4359-4370.
11. Li, X. C., Uchiyama, T., Raetz, C. R. H., and Hindsgaul, O. (2003) Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis, Org. Lett. 5, 539-541.
12. Jackman, J. E., Fierke, C. A., Tumey, L. N., Pirrung, M., Uchiyama, T., Tahir, S. H., Hindsgaul, O., and Raetz, C. R. H. (2000) Antibacterial agents that target lipid A biosynthesis in Gram-negative bacteria: Inhibition of diverse UDP-3-O-(R-3-hydroxymyristoyl)-N-acetyglucosamine deacetylases by substrate analogs containing zinc binding motifs, J. Biol. Chem. 275, 11002-11009.
13. Supuran, C. T., Casini, A., and Scozzafava, A. (2003) Protease inhibitors of the sulfonamide type: Anticancer, antiinflammatory, and antiviral agents, Med. Res. Rev. 23, 535-558.
14. Leung, D., Abbenante, G., and Fairlie, D. P. (2000) Protease inhibitors: Current status and future prospects, J. Med. Chem. 43, 305-341.
15. Supuran, C. T., Scozzafava, A., and Casini, A. (2003) Carbonic anhydrase inhibitors, Med. Res. Rev. 23, 146-189.
16. Whittington, D. A., Rusche, K. M., Shin, H., Fierke, C. A., and Christianson, D. W. (2003) Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis, PNAS 100, 8146-8150.
17. Coggins, B. E., Li, X. C., McClerren, A. L., Hindsgaul, O., Raetz, C. R. H., and Zhou, P. (2003) Structure of the LpxC deacetylase with a bound substrate-analog inhibitor, Nat. Struct. Biol. 10, 645-651.
18. Coggins, B. E., McClerren, A. L., Jiang, L., Li, X., Rudolph, J., Hindsgaul, O., Raetz, C. R. H., and Zhou, P. (2005) Refined solution structure of the LpxC-TU-514 complex and piCa analysis of an active site histidine: Insights into the mechanism and inhibitor design, Biochemistry 44, 1114-1126.
19. Gennadios, H. A., Whittington, D. A., Li, X., Fierke, C. A., and Christianson, D. W. (2006) Mechanistic inferences from the binding of ligands to LpxC, a metal-dependent deacetylase, Biochemistry 45, 7940-7948.
20. Young, K., Silver, L. L., Bramhill, D., Cameron, P., Eveland, S. S., Raetz, C. R. H., Hyland, S. A., and Anderson, M. S. (1995) The envA permeability cell division gene of Escherichia coli encodes the second enzyme of lipid A biosynthesis: UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase, J. Biol. Chem. 270, 30384-30391.
21. McClure, C. P., Rusche, K. M., Peariso, K., Jackman, J. E., Fierke, C. A., and Penner-Hahn, J. E. (2003) EXAFS studies of the zinc sites of UDP-(3-O-acyl)-N- acetylglucosamine deacetylase (LpxC), J. Inorg. Biochem. 94, 78-85.
22. Sorensen, P. G., Lutkenhaus, J., Young, K., Eveland, S. S., Anderson, M. S., and Raetz, C. R. H. (1996) Regulation of UDP-3-0- R-3-hydroxymyristoyl-N- acetylglucosamine deacetylase in Escherichia coli: The second enzymatic step of lipid a biosynthesis, J. Biol. Chem. 271, 25898-25905.
23. Okuyama, K., Hamamoto, T., Ishige, K., Takenouchi, K., and Noguchi, T. (2000) An efficient method for production of uridine 5′-diphospho-N- acetylglucosamine, Biosci. Biotechnol. Biochem. 64, 386-392.
24. Leiting, B., Pryor, K. D., Eveland, S. S., and Anderson, M. S. (1998) One-day enzymatic synthesis and purification of UDP-N-[1-C-14]acetyl- glucosamine, Anal. Biochem. 256, 185-191.
25. Harris, D. C. (1996) Quantitative Chemical Analysis, 4th ed., W. H. Freeman and Company, New York.
26. Benson, J. R., and Hare, P. E. (1975) Ortho-phthalaldehyde: Fluorogenic detection of primary amines in picomole range-Comparison with fluorescamine and ninhydrin, Proc. Natl. Acad. Sci. U.S.A. 72, 619-622.
27. McClerren, A. L., Zhou, P., Guan, Z., Raetz, C. R. H., and Rudolph, J. (2005) Kinetic analysis of the zinc-dependent deacetylase in the lipid A biosynthetic pathway, Biochemistry 44, 1106-1113.
28. Jackman, J. E., Raetz, C. R. H., and Fierke, C. A. (2001) Site-directed mutagenesis of the bacterial metalloamidase UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC). Identification of the zinc binding site, Biochemistry 40, 514-523.
29. Blasko, A., Bunton, C. A., Bunel, S., Ibarra, C., and Moraga, E. (1997) Determination of acid dissociation constants of anomers of amino sugars by 1H NMR spectroscopy, Carbohydr. Res. 298, 163-172.
30. Robitaille, P. M. L., Robitaille, P. A., Brown, G. G., and Brown, G. G. (1991) An analysis of the Ph-dependent chemical-shift behavior of phosphorus-containing metabolites, J. Magn. Reson. 92, 73-84.
31. Beall, B., and Lutkenhaus, J. (1987) Sequence-analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli, J. Bacteriol. 169, 5408-5415.
32. Normark, S., Boman, H. G., and Matsson, E. (1969) Mutant of Escherichia coli with anomalous cell division and ability to decrease episomally and chromosomally mediated resistance to ampicillin and several other antibiotics, J. Bacteriol. 97, 1334-1342.
33. Nishio, M., Umezawa, Y., Hirota, M., and Takeuchi, Y. (1995) The CH/p interaction: Significance in molecular recognition, Tetrahedron 51, 8665-8701.
34. Sujatha, M. S., and Balaji, P. V. (2004) Identification of common structural features of binding sites in galactose-specific proteins, Proteins: Struct., Funct., Genet. 55, 44-65.
35. Sujatha, M. S., Sasidhar, Y. U., and Balaji, P. V. (2004) Energetics of galactose- and glucose-aromatic amino acid interactions: Implications for binding in galactose-specific proteins, Protein Sci. 13, 2502-2514.
36. Mildvan, A. S., Weber, D. J., and Kuliopulos, A. (1992) Quantitative interpretations of double mutations of enzymes, Arch. Biochem. Biophys. 294, 327-340.
37. Mildvan, A. S. (2004) Inverse thinking about double mutants of enzymes, Biochemistry 43, 14517-14520.
38. Weber, D. J., Meeker, A. K., and Mildvan, A. S. (1991) Interactions of the acid and base catalysts on Staphylococcal nuclease as studied in a double mutant, Biochemistry 30, 6103-6114.
39. Hernick, M., and Fierke, C. A. (2006) Molecular recognition by E. coli UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase is modulated by bound metal ions, in press.
40. Li, X. C., McClerren, A. L., Raetz, C. R. H., and Hindsgaul, O. (2005) Mapping the active site of the bacterial enzyme LpxC using novel carbohydrate-based hydroxamic acid inhibitors, J. Carbohydr. Chem. 24, 583-609.