pKa calculations for class C ?-lactamases: The role of tyr-150

Author(s):  
Josette Lamotte-Brasseur ◽  
Alain Dubus ◽  
Rebecca C. Wade
Keyword(s):  
1999 ◽  
Vol 43 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Sonia Trépanier ◽  
James R. Knox ◽  
Natalie Clairoux ◽  
François Sanschagrin ◽  
Roger C. Levesque ◽  
...  

ABSTRACT Site-directed mutagenesis of Ser-289 of the class C β-lactamase from Enterobacter cloacae P99 was performed to investigate the role of this residue in β-lactam hydrolysis. This amino acid lies near the active site of the enzyme, where it can interact with the C-3 substituent of cephalosporins. Kinetic analysis of six mutant β-lactamases with five cephalosporins showed that Ser-289 can be substituted by amino acids with nonpolar or polar uncharged side chains without altering the catalytic efficiency of the enzyme. These data suggest that Ser-289 is not essential in the binding or hydrolytic mechanism of AmpC β-lactamase. However, replacement by Lys or Arg decreased by two- to threefold the k cat of four of the five β-lactams tested, particularly cefoperazone, cephaloridine, and cephalothin. Three-dimensional models of the mutant β-lactamases revealed that the length and positive charge of the side chain of Lys and Arg could create an electrostatic linkage to the C-4 carboxylic acid group of the dihydrothiazine ring of the acyl intermediate which could slow the deacylation step or hinder release of the product.


2010 ◽  
Vol 54 (8) ◽  
pp. 3484-3488 ◽  
Author(s):  
José-Manuel Rodríguez-Martínez ◽  
Patrice Nordmann ◽  
Esthel Ronco ◽  
Laurent Poirel

ABSTRACT An AmpC-type β-lactamase conferring high-level resistance to expanded-spectrum cephalosporins and monobactams was characterized from an Acinetobacter baumannii clinical isolate. This class C β-lactamase (named ADC-33) possessed a Pro210Arg substitution together with a duplication of an Ala residue at position 215 (inside the Ω-loop) compared to a reference AmpC cephalosporinase from A. baumannii. ADC-33 hydrolyzed ceftazidime, cefepime, and aztreonam at high levels, which allows the classification of this enzyme as an extended-spectrum AmpC (ESAC). Site-directed mutagenesis confirmed the role of both substitutions in its ESAC property.


2021 ◽  
Author(s):  
Yansong Li ◽  
Guoliang Chen ◽  
Jing Lv ◽  
Zhao Dong ◽  
Rongfei Wang ◽  
...  

Abstract Background: Resting-state EEG microstates are thought to reflect brief activations of several interacting components of resting-state brain networks. Surprisingly, we still know little about the role of these microstates in migraine. In the present study, we attempted to address this issue by examining EEG microstates in patients with migraine without aura (MwoA) during the interictal period and comparing them with those of a group of healthy controls (HC). Methods: Resting-state EEG was recorded in 61 MwoA patients (50 females) and 66 HC (50 females). Microstate parameters were compared between the two groups. We computed four widely identified canonical microstate classes A-D.Results: Microstate classes B and D displayed higher time coverage and occurrence in the MwoA patient group than in the HC group, while microstate class C exhibited significantly lower time coverage and occurence in the MwoA patient group. Meanwhile, the mean duration of microstate class C was significantly shorter in the MwoA patient group than in the HC group. Moreover, among the MwoA patient group, the duration of microstate class C correlated negatively with clinical measures of headache‐related disability as assessed by the six-item Headache Impact Test (HIT-6). Finally, microstate syntax analysis showed significant differences in transition probabilities between the two groups, primarily involving microstate classes B, C and D. Conclusions: By exploring EEG microstate characteristics at baseline we were able to explore the neurobiological mechanisms underlying altered cortical excitability and aberrant sensory, affective and cognitive processing, thus deepening our understanding of migraine pathophysiology.


2017 ◽  
Vol 280 ◽  
pp. S121
Author(s):  
Fatma Yıldız ◽  
İ. İpek Boşgelmez ◽  
M. Serdar Kütük

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Brad Wallar ◽  
Brianne Docter ◽  
David Leonard ◽  
Rachel Powers
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document