Understanding the role of conserved disulfide bridge in class A Beta lactamase Ftu-1 from Fransicella tulerensis

Abstract

FTU-1 shares about 21 to 34% amino acid sequence identity with the other class A β-lactamases and it harbors two cysteine residues conserved similarily in all class A carbapenemases. Thus, FTU-1 is the first weak class A carbapenemase that is native to gram-negative Francisella tularensis. These enzymes have relatively low amino acid identity with “classical” class A β-lactamases and harbor two characteristic cysteine residues at Ambler positions 69, directly preceding the active site serine, and 238, which follows two resides after the conserved KTG motif. These cysteine residues form a disulfide bridge which serves to connect the two domains of the enzyme. FTU-1 shares the amino acid sequence identity with the class A β-lactamases BES-1 (33.8%), CTX-M-38 (30.8%), VEB 1(29.3%), SHV-1 (26.4%), TEM-1 (24.2%), and PER-1 (21.3%). Compared to other class A carbapenemases, FTU-1 shares 35.0% amino acid identity with NMC-A, 34.9% with KPC-2, 34.4% with SME-1, 32.4% with SFC-1 from Serratia fonticola, 32.3% with BIC-1 from Pseudomonas fluorescens, 29% with BEL-1 from Pseudomonas aeruginosa, and 26.7% with GES-1. This low amino acid identities of FTU-1 with other class A β-lactamases, including the carbapenemases, indicates that FTU-1 constitutes a new distinct branch of class A β-lactamases.