skip to content

Polymer Program Title

James R. Knox

Professor Emeritus of Molecular and Cell Biology (Biophysics)

Education

Ph.D. Boston University
B.S. University of Missouri at Rolla

Contact Information

Phone: (860) 486-3133
Email: knox@mail.ims.uconn.edu
Website: http://www.mcb.uconn.edu/fac.php?name=knoxj

Research Interests

Atomic Level Structures of Cell-Wall Synthesizing Enzymes

X-ray crystallography is being employed to establish the atomic-level structure of ligase enzymes which build the polymeric bacterial wall and are potential molecular targets for new inhibitory drugs. One of the enzymes is the cause of a new bacterial resistance to vancomycin-type antibiotics. The work is in collaboration with C.T. Walsh, Harvard Medical School. (Supported by the NIH.)

Atomic Level Structures of Penicillinase Enzymes by X-Ray Crystallography

The three-dimensional structure of three types of penicillinase have been determined to high resolution, and work on mutant penicillinases is in progress. We hope to suggest ways of designing new penicillin and cephalosporin antibiotics which will be less susceptible to break-down by the enzyme defenses of penicillin-resistant bacteria. (Supported by Wyeth-Ayerst Research, NIH, and the Veterans Administration.)

Recent Publications

  1. Knox, J. R. 2009. Before Our Time: Early ß-Lactamase Papers and the People Who Wrote Them. Book chapter to be published by Nova Science Publishers, Ed. J.-M. Frere.
  2. Nukaga, M., C. R. Bethel, J. M. Thomson, A. M. Hujer, A. Distler, V. E. Anderson, J. R. Knox and R. A. Bonomo. 2008. Inhibition of class A ß-lactamases by carbapenems: Crystallographic observation of two conformations of meropenem in SHV-1. J. Am. Chem. Soc. 130: 12656–12662.
  3. Venkatesan, A. M., et al. D. M. Shlaes, J. R. Knox and T. S. Mansour. 2006. Structure-activity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum ß-lactamase inhibitors: Evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods. J. Med. Chem. 49: 4623-4637
  4. Sun, T., C. R. Bethe, R. A. Bonomo and J. R. Knox. 2004. Inhibitor-Resistant Class A ß-Lactamases: Consequences of the ser130-to-glycine mutation seen in apo and tazobactam structures of the SHV-1 variant. Biochemistry 43: 14111-14117.
  5. Nukaga, M., T. Abe, A. M. Venkatesan, T. S. Mansour, A. H. Hujer, R. A. Bonomo and J. R. Knox. 2004. Structure-Activity Relationship of 6-Methylidene Penems Bearing Tricyclic Heterocycles as Broad-Spectrum ß-Lactamase Inhibitors: Crystallographic Structures Show Unexpected Binding of 1,4-Thiazepine Intermediates. J. Med. Chem. 47: 6556-6568.
  6. Murthy, N. S. and J. R. Knox. 2004. Hydration of Proteins: SAXS study of native and methoxy-polyethyleneglycol (mPEG)-modified L-asparaginase and bovine serum albumin in mPEG solutions. Biopolymers 74: 457-466.
  7. Nukaga. M., S. Kumar, K. Nukaga, R. F. Pratt and J. R. Knox..2004. Hydrolysis of third-generation cephalosporins by class C ß-lactamases: Structures of a transition-state analog of cefotaxime in wild-type and extended-spectrum enzymes. J. Biol. Chem. 279: 9344-9352.
  8. Nukaga, M., T. Abe, A. M. Venkatesan, T. S. Mansour, R. A. Bonomo and J. R. Knox. 2003. Inhibition of class A and class C ß-lactamases by penems: Crystallographic structures of a novel 1,4-thiazepine intermediate. Biochemistry 42: 13152-13159.
  9. Nukaga, M., K. Mayama, A. Hujer, R. A. Bonomo and J. R. Knox. 2003. Ultrahigh resolution structure of a class A ß-lactamase: On the mechanism and specificity of the extended-spectrum SHV-2 enzyme. J. Mol. Biol. 328: 289-301.
  10. Sun, T., M. Nukaga, K. Mayama, E. H. Braswell and J. R. Knox. 2003. Comparison of ß-lactamases of classes A and D: 1.5 Å crystallographic structure of the class D OXA-1 oxacillinase. Prot. Sci. 12: 82-91.

Polymer Program: 860.486.3582: polymer@ims.uconn.edu