Outer Membrane Phospholipase A Dimer Stability Does Not Correlate to Occluded Surface Area†

Biochemistry ◽  
2008 ◽  
Vol 47 (46) ◽  
pp. 12095-12103 ◽  
Author(s):  
Alexandra Ebie Tan ◽  
Karen G. Fleming
Keyword(s):  
Outer Membrane ◽  
Surface Area ◽  
Phospholipase A ◽  
Outer Membrane Phospholipase A

scholarly journals Absence of the Outer Membrane Phospholipase A Suppresses the Temperature-Sensitive Phenotype of Escherichia coli degPMutants and Induces the Cpx and ςE Extracytoplasmic Stress Responses

2001 ◽  
Vol 183 (18) ◽  
pp. 5230-5238 ◽  
Author(s):  
Geoffrey R. Langen ◽  
Jill R. Harper ◽  
Thomas J. Silhavy ◽  
S. Peter Howard
Keyword(s):  
Escherichia Coli ◽  
Outer Membrane ◽  
Stress Responses ◽  
Elevated Temperatures ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Phospholipase A ◽  
Temperature Sensitive ◽  
Outer Membrane Phospholipase A ◽  
Temperature Sensitive Phenotype

ABSTRACT DegP is a periplasmic protease that is a member of both the ςE and Cpx extracytoplasmic stress regulons ofEscherichia coli and is essential for viability at temperatures above 42°C. [U-14C]acetate labeling experiments demonstrated that phospholipids were degraded indegP mutants at elevated temperatures. In addition, chloramphenicol acetyltransferase, β-lactamase, and β-galactosidase assays as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that large amounts of cellular proteins are released from degP cells at the nonpermissive temperature. A mutation in pldA, which encodes outer membrane phospholipase A (OMPLA), was found to rescue degPcells from the temperature-sensitive phenotype. pldA degP mutants had a normal plating efficiency at 42°C, displayed increased viability at 44°C, showed no degradation of phospholipids, and released far lower amounts of cellular protein to culture supernatants. degP and pldA degP mutants containing chromosomal lacZ fusions to Cpx and ςE regulon promoters indicated that both regulons were activated in the pldA mutants. The overexpression of the envelope lipoprotein, NlpE, which induces the Cpx regulon, was also found to suppress the temperature-sensitive phenotype ofdegP mutants but did not prevent the degradation of phospholipids. These results suggest that the absence of OMPLA corrects the degP temperature-sensitive phenotype by inducing the Cpx and ςE regulons rather than by inactivating the phospholipase per se.

scholarly journals Topology of the outer membrane phospholipase A of Salmonella typhimurium.

1997 ◽  
Vol 179 (11) ◽  
pp. 3443-3450 ◽  
Author(s):  
K B Merck ◽  
H de Cock ◽  
H M Verheij ◽  
J Tommassen
Keyword(s):  
Salmonella Typhimurium ◽  
Outer Membrane ◽  
Phospholipase A ◽  
Outer Membrane Phospholipase A

Substrate interferes with dimerisation of outer membrane phospholipase A

FEBS Letters ◽  
2002 ◽  
Vol 516 (1-3) ◽  
pp. 31-34 ◽  
Author(s):  
Roelie L Kingma ◽  
Maarten R Egmond
Keyword(s):  
Outer Membrane ◽  
Phospholipase A ◽  
Outer Membrane Phospholipase A

Kinetic characterization of Escherichia coli outer membrane phospholipase A using mixed detergent-lipid micelles

Biochemistry ◽  
1989 ◽  
Vol 28 (3) ◽  
pp. 1139-1147 ◽  
Author(s):  
Anton J. G. Horrevoets ◽  
Tilman M. Hackeng ◽  
Hubertus M. Verheij ◽  
Ruud Dijkman ◽  
Gerard H. De Haas
Keyword(s):  
Escherichia Coli ◽  
Outer Membrane ◽  
Phospholipase A ◽  
Kinetic Characterization ◽  
Outer Membrane Phospholipase A ◽  
Lipid Micelles

scholarly journals Crystal structure of calcium bound outer membrane phospholipase A (OmpLA) from Salmonella typhi and in silico anti-microbial screening

2020 ◽  
Author(s):  
Perumal Perumal ◽  
Rahul Raina ◽  
Sundara Baalaji Narayanan ◽  
Arulandu Arockiasamy
Keyword(s):  
Crystal Structure ◽  
Outer Membrane ◽  
In Silico ◽  
Membrane Integrity ◽  
Acid Tolerance ◽  
Salmonella Typhi ◽  
Phospholipase A ◽  
Gram Negative ◽  
Activated State ◽  
Outer Membrane Phospholipase A

AbstractAntimicrobial resistance is widespread in Salmonella infections that affect millions worldwide. Salmonella typhi and other Gram-negative bacterial pathogens encode an outer membrane phospholipase A (OmpLA), crucial for their membrane integrity. Further, OmpLA is implicated in pathogen internalization, haemolysis, acid tolerance, virulence and sustained infection in human hosts. OmpLA is an attractive drug target for developing novel anti-microbials that attenuate virulence, as the abrogation of OmpLA encoding pldA gene causes loss of virulence. Here, we present the crystal structure of Salmonella typhi OmpLA in dimeric calcium bound activated state at 2.95 Å. Structure analysis suggests that OmpLA is a potential druggable target. Further, we have identified and shortlisted small molecules that bind at the dimer interface using structure based in silico screening, docking and molecular dynamics. While it requires further experimental validation, anti-microbial discovery targeting OmpLA from gram-negative pathogens offers an advantage as OmpLA is required for virulence.

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