Clarke, Fumihiro Kawai, Sam-Yong Park, Jeremy R. Neisseria gonorrhoeae Penicillin-Binding Protein 3 Demonstrates a Pronounced Preference for NОµ-Acylated Substrates. Synthesis and Evaluation of 3-(Dihydroxyboryl)benzoic Acids as d,d-Carboxypeptidase R39 Inhibitors. Woon, Thomas Gerards, Nathalie Teller, Delphine S. Molecular and Structural Analysis of Mosaic Variants of Penicillin-Binding Protein 2 Conferring Decreased Susceptibility to Expanded-Spectrum Cephalosporins in Neisseria gonorrhoeae: Role of Epistatic Mutations. Joshua Tomberg, Magnus Unemo, Christopher Davies, and Robert A.Natural and Synthetic Small Boron-Containing Molecules as Potential Inhibitors of Bacterial and Fungal Quorum Sensing. Dembitsky, Abed Al Aziz Al Quntar, and Morris Srebnik. A Highly Conserved Interaction Involving the Middle Residue of the SXN Active-Site Motif Is Crucial for Function of Class B Penicillin-Binding Proteins: Mutational and Computational Analysis of PBP 2 from N. Joshua Tomberg, Brenda Temple, Alena Fedarovich, Christopher Davies, and Robert A.Structural Effect of the Asp345a Insertion in Penicillin-Binding Protein 2 from Penicillin-Resistant Strains of Neisseria gonorrhoeae. Alena Fedarovich, Edward Cook, Joshua Tomberg, Robert A.A Variable Active Site Residue Influences the Kinetics of Response Regulator Phosphorylation and Dephosphorylation. Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness. Jerse, Magnus Unemo, Christopher Davies, and Robert A. Joshua Tomberg, Alena Fedarovich, Leah R.Molecular Features of Cephalosporins Important for Activity against Antimicrobial-Resistant Neisseria gonorrhoeae. This article is cited by 40 publications. gonorrhoeae, resulted in a decreased growth rate and marked morphological abnormalities. gonorrhoeae, although deletion of both PBP 3 and PBP 4, the other low-molecular-mass PBP in N. Deletion of PBP 3 alone had little effect on viability, growth rate, and morphology of N. PBP 3 displayed weak transpeptidase activity in a model transpeptidase reaction but was active as an endopeptidase, cleaving dimeric peptide cross-links. The pH dependence profiles of both carboxypeptidase activity and ОІ-lactam acylation were bell-shaped with maximal activity at pH 8.0в€’8.5. Activity against a в€ј d-Ala- d-Lac peptide substrate was в€ј2-fold lower than against the analogous в€ј d-Ala- d-Ala peptide substrate, indicating that deacylation is rate determining for both amide and ester hydrolysis. This is the highest k cat value yet reported for a PBP or other serine peptidases. PBP 3 also demonstrated exceptionally high carboxypeptidase activity with a k cat of 580 s - 1 and a k cat /K m of 1.8 Г— 10 5 M - 1 s - 1 with the substrate N О±-Boc- N Оµ-Cbz- l-Lys- d-Ala- d-Ala.

PBP 3 had an unusually high k 2 /KвЂ value relative to other PBPs for acylation with penicillin (7.7 Г— 10 5 M - 1 s - 1) at pH 8.5 at 25 вЊ and hydrolyzed bound antibiotic very slowly ( k 3 230 min). A soluble form of penicillin-binding protein 3 (PBP 3) from Neisseria gonorrhoeae was expressed and purified from Escherichia coli and characterized for its interaction with ОІ-lactam antibiotics, its catalytic properties with peptide and peptidoglycan substrates, and its role in cell viability and morphology.

Pbp3 neisseria