This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rudgers, G. W.
Right arrow Articles by Palzkill, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rudgers, G. W.
Right arrow Articles by Palzkill, T.

Next Article 

Antimicrobial Agents and Chemotherapy, December 2001, p. 3279-3286, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3279-3286.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Binding Properties of a Peptide Derived from beta -Lactamase Inhibitory Protein

Gary W. Rudgers,1 Wanzhi Huang,1 and Timothy Palzkill1,2,*

Department of Molecular Virology & Microbiology1 and Department of Biochemistry,2 Baylor College of Medicine, Houston, Texas 77030

Received 28 February 2001/Returned for modification 11 July 2001/Accepted 29 August 2001

To overcome the antibiotic resistance mechanism mediated by beta -lactamases, small-molecule beta -lactamase inhibitors, such as clavulanic acid, have been used. This approach, however, has applied selective pressure for mutations that result in beta -lactamases no longer sensitive to beta -lactamase inhibitors. On the basis of the structure of beta -lactamase inhibitor protein (BLIP), novel peptide inhibitors of beta -lactamase have been constructed. BLIP is a 165-amino-acid protein that is a potent inhibitor of TEM-1 beta -lactamase (Ki = 0.3 nM). The cocrystal structure of TEM-1 beta -lactamase and BLIP indicates that residues 46 to 51 of BLIP make critical interactions with the active site of TEM-1 beta -lactamase. A peptide containing this six-residue region of BLIP was found to retain sufficient binding energy to interact with TEM-1 beta -lactamase. Inhibition assays with the BLIP peptide reveal that, in addition to inhibiting TEM-1 beta -lactamase, the peptide also inhibits a class A beta -lactamase and a class C beta -lactamase that are not inhibited by BLIP. The crystal structures of class A and C beta -lactamases and two penicillin-binding proteins (PBPs) reveal that the enzymes have similar three-dimensional structures in the vicinity of the active site. This similarity suggests that the BLIP peptide inhibitor may have a broad range of activity that can be used to develop novel small-molecule inhibitors of various classes of beta -lactamases and PBPs.

* Corresponding author. Mailing address: Department of Molecular Virology & Microbiology, Baylor College of Medicine, One Baylor Plaza, BCMD Rm. 221D, Mailstop BCM-280, Houston, TX 77030-3498. Phone: (713) 798-5609. Fax: (713) 798-7375. E-mail: timothyp{at}bcm.tmc.edu.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3279-3286, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3279-3286.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wang, J., Palzkill, T., Chow, D.-C. (2009). Structural Insight into the Kinetics and {Delta}Cp of Interactions between TEM-1 {beta}-Lactamase and {beta}-Lactamase Inhibitory Protein (BLIP). J. Biol. Chem. 284: 595-609 [Abstract] [Full Text]  
  • Wang, J., Zhang, Z., Palzkill, T., Chow, D.-C. (2007). Thermodynamic Investigation of the Role of Contact Residues of beta-Lactamase-inhibitory Protein for Binding to TEM-1 beta-Lactamase. J. Biol. Chem. 282: 17676-17684 [Abstract] [Full Text]  
  • Reynolds, K. A., Thomson, J. M., Corbett, K. D., Bethel, C. R., Berger, J. M., Kirsch, J. F., Bonomo, R. A., Handel, T. M. (2006). Structural and Computational Characterization of the SHV-1 beta-Lactamase-beta-Lactamase Inhibitor Protein Interface. J. Biol. Chem. 281: 26745-26753 [Abstract] [Full Text]  
  • Huang, W., Beharry, Z., Zhang, Z., Palzkill, T. (2003). A broad-spectrum peptide inhibitor of {beta}-lactamase identified using phage display and peptide arrays. Protein Eng Des Sel 16: 853-860 [Abstract] [Full Text]  
  • Schroeder, W. A., Locke, T. R., Jensen, S. E. (2002). Resistance to {beta}-Lactamase Inhibitor Protein Does Not Parallel Resistance to Clavulanic Acid in TEM {beta}-Lactamase Mutants. Antimicrob. Agents Chemother. 46: 3568-3573 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»