JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M004471200 on August 30, 2000

J. Biol. Chem., Vol. 276, Issue 1, 616-623, January 5, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/1/616    most recent
M004471200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Davies, C.
Right arrow Articles by Nicholas, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davies, C.
Right arrow Articles by Nicholas, R. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Crystal Structure of a Deacylation-defective Mutant of Penicillin-binding Protein 5 at 2.3-Å Resolution*

Christopher DaviesDagger , Stephen W. White§, and Robert A. Nicholas||**

From the Dagger  School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, § Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,  Department of Biochemistry, University of Tennessee, Memphis, Tennessee 38163, and || Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365

Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a D-alanine carboxypeptidase, cleaving the C-terminal D-alanine residue from cell wall peptides. Like all PBPs, PBP 5 forms a covalent acyl-enzyme complex with beta -lactam antibiotics; however, PBP 5 is distinguished by its high rate of deacylation of the acyl-enzyme complex (t1/2 ~ 9 min). A Gly-105 right-arrow Asp mutation in PBP 5 markedly impairs this beta -lactamase activity (deacylation), with only minor effects on acylation, and promotes accumulation of a covalent complex with peptide substrates. To gain further insight into the catalytic mechanism of PBP 5, we determined the three-dimensional structure of the G105D mutant form of soluble PBP 5 (termed sPBP 5') at 2.3 Å resolution. The structure is composed of two domains, a penicillin binding domain with a striking similarity to Class A beta -lactamases (TEM-1-like) and a domain of unknown function. In addition, the penicillin-binding domain contains an active site loop spatially equivalent to the Omega  loop of beta -lactamases. In beta -lactamases, the Omega  loop contains two amino acids involved in catalyzing deacylation. This similarity may explain the high beta -lactamase activity of wild-type PBP 5. Because of the low rate of deacylation of the G105D mutant, visualization of peptide substrates bound to the active site may be possible.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and the structure factors (code 1hd8) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

** To whom correspondence should be addressed: Dept. of Pharmacology, CB#7365 Mary Ellen Jones Bldg., Chapel Hill, NC 27599-7365. E-mail: nicholas@med.unc.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
M. Suvorov, S. B. Vakulenko, and S. Mobashery
Cytoplasmic-Membrane Anchoring of a Class A {beta}-Lactamase and Its Capacity in Manifesting Antibiotic Resistance
Antimicrob. Agents Chemother., August 1, 2007; 51(8): 2937 - 2942.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
D.-J. Scheffers and M. G. Pinho
Bacterial Cell Wall Synthesis: New Insights from Localization Studies
Microbiol. Mol. Biol. Rev., December 1, 2005; 69(4): 585 - 607.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Sauvage, R. Herman, S. Petrella, C. Duez, F. Bouillenne, J.-M. Frere, and P. Charlier
Crystal Structure of the Actinomadura R39 DD-peptidase Reveals New Domains in Penicillin-binding Proteins
J. Biol. Chem., September 2, 2005; 280(35): 31249 - 31256.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Morlot, L. Pernot, A. Le Gouellec, A. M. Di Guilmi, T. Vernet, O. Dideberg, and A. Dessen
Crystal Structure of a Peptidoglycan Synthesis Regulatory Factor (PBP3) from Streptococcus pneumoniae
J. Biol. Chem., April 22, 2005; 280(16): 15984 - 15991.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. S. Wilke, T. L. Hills, H.-Z. Zhang, H. F. Chambers, and N. C. J. Strynadka
Crystal Structures of the Apo and Penicillin-acylated Forms of the BlaR1 {beta}-Lactam Sensor of Staphylococcus aureus
J. Biol. Chem., November 5, 2004; 279(45): 47278 - 47287.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. A. Nicholas, S. Krings, J. Tomberg, G. Nicola, and C. Davies
Crystal Structure of Wild-type Penicillin-binding Protein 5 from Escherichia coli: IMPLICATIONS FOR DEACYLATION OF THE ACYL-ENZYME COMPLEX
J. Biol. Chem., December 26, 2003; 278(52): 52826 - 52833.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. S. Ghosh and K. D. Young
Sequences near the Active Site in Chimeric Penicillin Binding Proteins 5 and 6 Affect Uniform Morphology of Escherichia coli
J. Bacteriol., April 1, 2003; 185(7): 2178 - 2186.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
C. Goffin and J.-M. Ghuysen
Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent
Microbiol. Mol. Biol. Rev., December 1, 2002; 66(4): 702 - 738.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. K. Deka, M. Machius, M. V. Norgard, and D. R. Tomchick
Crystal Structure of the 47-kDa Lipoprotein of Treponema pallidum Reveals a Novel Penicillin-binding Protein
J. Biol. Chem., October 25, 2002; 277(44): 41857 - 41864.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
D. E. Nelson, A. S. Ghosh, A. L. Paulson, and K. D. Young
Contribution of Membrane-Binding and Enzymatic Domains of Penicillin Binding Protein 5 to Maintenance of Uniform Cellular Morphology of Escherichia coli
J. Bacteriol., July 1, 2002; 184(13): 3630 - 3639.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
H. C.F. Cote, Z. L. Brumme, K. J.P. Craib, C. S. Alexander, B. Wynhoven, L. Ting, H. Wong, M. Harris, P. R. Harrigan, M. V. O'Shaughnessy, et al.
Changes in Mitochondrial DNA as a Marker of Nucleoside Toxicity in HIV-Infected Patients
N. Engl. J. Med., March 14, 2002; 346(11): 811 - 820.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
D. E. Nelson and K. D. Young
Contributions of PBP 5 and DD-Carboxypeptidase Penicillin Binding Proteins to Maintenance of Cell Shape in Escherichia coli
J. Bacteriol., May 15, 2001; 183(10): 3055 - 3064.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.