Crystal structures of penicillin-binding protein 3 in complexes with azlocillin and cefoperazone in both acylated and deacylated forms

FEBS Letters
Jingshan RenRaymond J Owens

Abstract

Penicillin-binding protein 3 (PBP3) from Pseudomonas aeruginosa is the molecular target of β-lactam-based antibiotics. Structures of PBP3 in complexes with azlocillin and cefoperazone, which are in clinical use for the treatment of pseudomonad infections, have been determined to 2.0 Å resolution. Together with data from other complexes, these structures identify a common set of residues involved in the binding of β-lactams to PBP3. Comparison of wild-type and an active site mutant (S294A) showed that increased thermal stability of PBP3 following azlocillin binding was entirely due to covalent binding to S294, whereas cefoperazone binding produces some increase in stability without the covalent link. Consistent with this, a third crystal structure was determined in which the hydrolysis product of cefoperazone was noncovalently bound in the active site of PBP3. This is the first structure of a complex between a penicillin-binding protein and cephalosporic acid and may be important in the design of new noncovalent PBP3 inhibitors.

References

Aug 1, 1979·Antimicrobial Agents and Chemotherapy·H C NeuK Kung
Dec 5, 1998·Microbiology and Molecular Biology Reviews : MMBR·C Goffin, J M Ghuysen
May 26, 2005·Protein Expression and Purification·F William Studier
Feb 13, 2008·FEMS Microbiology Reviews·Eric SauvagePaulette Charlier
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·Dominika BorekZbyszek Otwinowski
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 16, 2010·Antimicrobial Agents and Chemotherapy·Bartolomé MoyáAntonio Oliver
Jun 29, 2010·Protein Expression and Purification·Sandra Ruiloba de LeónAnthony J Clarke
Dec 8, 2010·Proceedings of the National Academy of Sciences of the United States of America·Seungil HanVeerabahu Shanmugasundaram
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Jul 1, 2008·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·József Szeberényi
Oct 26, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Astrid ZervosenAndré Luxen
Jan 26, 2013·Annals of the New York Academy of Sciences·George H Talbot
Aug 1, 2013·ACS Chemical Biology·Sander S van BerkelChristopher J Schofield
May 31, 2014·PloS One·Eric SauvagePaulette Charlier

❮ Previous
Next ❯

Citations

Aug 1, 2019·The Journal of Biological Chemistry·Avinash SinghChristopher Davies
Mar 11, 2020·Antimicrobial Agents and Chemotherapy·Vijay KumarFocco van den Akker
Mar 4, 2020·Scientific Reports·Venkata Raveendra PothineniJayakumar Rajadas

❮ Previous
Next ❯

Methods Mentioned

BETA
size exclusion chromatography
deacylation
thermal shift

Software Mentioned

MOLREP
COOT
HKL2000
CCP4 suite
PHENIX

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.