scholarly journals Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nagakumar Bharatham ◽  
Purnendu Bhowmik ◽  
Maho Aoki ◽  
Ui Okada ◽  
Sreevalli Sharma ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Efflux Pump ◽  
Binding Pocket ◽  
Structural Features ◽  
Multi Drug Resistance ◽  
Salmonella Spp ◽  
Resistance Nodulation Division ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

AbstractOqxB is an RND (Resistance-Nodulation-Division) efflux pump that has emerged as a factor contributing to the antibiotic resistance in Klebsiella pneumoniae. OqxB underwent horizontal gene transfer and is now seen in other Gram-negative bacterial pathogens including Escherichia coli, Enterobacter cloacae and Salmonella spp., further disseminating multi-drug resistance. In this study, we describe crystal structure of OqxB with n-dodecyl-β-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 Å resolution. We utilize this structure in computational studies to predict the key amino acids contributing to the efflux of fluoroquinolones by OqxB, distinct from analogous residues in related transporters AcrB and MexB. Finally, our complementation assays with mutated OqxB and minimum inhibitory concentration (MIC) experiments with clinical isolates of E. coli provide further evidence that the predicted structural features are indeed involved in ciprofloxacin efflux.

scholarly journals Structure-function studies of CrmK, an oxidase involved in Caerulomycin A biosynthesis

2014 ◽  
Vol 70 (a1) ◽  
pp. C1669-C1669
Author(s):  
Marie-Ève Picard ◽  
Julie Barma ◽  
Yiguang Zhu ◽  
Xavier Murphy Després ◽  
Jean-Baptiste Duvignaud ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Pocket ◽  
Antimicrobial Activities ◽  
Active Site Residues ◽  
Covalent Bonds ◽  
Protein Residues ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

Caerulomycin A (CRM A) is an immunosupressive agent that has a unique 2,2'-bipyridine core structure. Isolated from a marine-derived Actinoalloteichus cyanogriseus, this natural product exhibits antifungal, anti-amoebic, antitumor, and antimicrobial activities. Its biosynthetic pathway consists of more than 20 enzymes, at least seven of which are putatively involved in post-PKS/NRPS modifications of the scaffold. Among these, CrmK is a flavin-dependent oxidase. We have determined the crystal structure of CrmK bound to its flavin adenin dinucleotide (FAD) cofactor at 1.9 Å resolution. FAD linkage to CrmK is observed via two covalent bonds with protein residues His64 and Cys124. This crystal structure, combined with the activity analysis of both wild-type CrmK and a series of mutants, has revealed the role of active site residues lining the substrate and FAD binding pocket. Our studies add additional molecular insights into the structure and function relationship of the bicovalently flavinylated oxidases.

Single-Molecule Force Spectroscopy of Transmembrane β-Barrel Proteins

2018 ◽  
Vol 11 (1) ◽  
pp. 375-395 ◽  
Author(s):  
Johannes Thoma ◽  
K. Tanuj Sapra ◽  
Daniel J. Müller
Keyword(s):  
Single Molecule ◽  
Force Spectroscopy ◽  
General Mechanism ◽  
Dynamic Mode ◽  
Single Molecule Force Spectroscopy ◽  
Force Relaxation ◽  
Sequential Unfolding ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

Single-molecule force spectroscopy (SMFS) has been widely applied to study the mechanical unfolding and folding of transmembrane proteins. Here, we review the recent progress in characterizing bacterial and human transmembrane β-barrel proteins by SMFS. First, we describe the mechanical unfolding of transmembrane β-barrels, which follows a general mechanism dictated by the sequential unfolding and extraction of individual β-strands and β-hairpins from membranes. Upon force relaxation, the unfolded polypeptide can insert stepwise into the membrane as single β-strands or β-hairpins to fold as the native β-barrel. The refolding can be followed at a high spatial and temporal resolution, showing that small β-barrels are able to fold without assistance, whereas large and complex β-barrels require chaperone cofactors. Applied in the dynamic mode, SMFS can quantify the kinetic and mechanical properties of single β-hairpins and reveal complementary insight into the membrane protein structure and function relationship. We further outline the challenges that SMFS experiments must overcome for a comprehensive understanding of the folding and function of transmembrane β-barrel proteins.

In Silico Identification for α-Amino-ε-Caprolactam Racemases by Using Information on the Structure and Function Relationship

2015 ◽  
Vol 176 (5) ◽  
pp. 1303-1314 ◽  
Author(s):  
Wisarut Payoungkiattikun ◽  
Seiji Okazaki ◽  
Shogo Nakano ◽  
Atsutoshi Ina ◽  
Aran H-Kittikun ◽  
...  
Keyword(s):  
In Silico ◽  
Structure And Function ◽  
In Silico Identification ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation

Biochemistry ◽  
2011 ◽  
Vol 50 (39) ◽  
pp. 8352-8361 ◽  
Author(s):  
Alessia Belgi ◽  
Mohammed A. Hossain ◽  
Fazel Shabanpoor ◽  
Linda Chan ◽  
Suode Zhang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structure And Function ◽  
C Terminus ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of
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