Dataset Information

Proteomics and Docking Study Targeting Penicillin-Binding Protein and Penicillin-Binding Protein2a of Methicillin-Resistant Staphylococcus aureus Strain SO-1977 Isolated from Sudan.

ABSTRACT: Whole genome sequencing of methicillin-resistant Staphylococcus aureus (MRSA) strain isolated from Sudan has led to a great deal of information, which allows the identification and characterization of some pivotal proteins. The objective of this study was to investigate the penicillin-binding proteins, PBP and PBP2a, of SO-1977 strain to have insights about their physicochemical properties and to assess and describe the interaction of some phytochemicals against them in silico. PBP and PBP2a from MRSA's Sudan strain were found to be of great resemblance with some other strains. G246E single-nucleotide polymorphism was reported and identified in the allosteric binding site positioned in the non-penicillin-binding domain. The docked compounds demonstrated good binding energies and hydrogen bond interactions with residue Ser404 which plays crucial roles in ?-lactam activity. This finding would contribute significantly to designing effective ?-lactam drugs, to combat and treat ?-lactam-resistant bacteria in the future.

SUBMITTER: Mohamed SB

PROVIDER: S-EPMC6637844 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Proteomics and Docking Study Targeting Penicillin-Binding Protein and Penicillin-Binding Protein2a of Methicillin-Resistant <i>Staphylococcus aureus</i> Strain SO-1977 Isolated from Sudan.

Mohamed Sofia B SB Adlan Talal A TA Khalafalla Nagla A NA Abdalla Nusiba I NI Ali Zainab Sa ZS Munir Ka Abdella A Hassan Mohamed M MM Elnour Mohammed-Ahmed B MB

Evolutionary bioinformatics online 20190716

Whole genome sequencing of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strain isolated from Sudan has led to a great deal of information, which allows the identification and characterization of some pivotal proteins. The objective of this study was to investigate the penicillin-binding proteins, PBP and PBP2a, of SO-1977 strain to have insights about their physicochemical properties and to assess and describe the interaction of some phytochemicals against them in silico. PBP and PB ...[more]

PMID: 31360059

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Project description:The mechanism of the ?-lactam antibacterials is the functionally irreversible acylation of the enzymes that catalyze the cross-linking steps in the biosynthesis of their peptidoglycan cell wall. The Gram-positive pathogen Staphylococcus aureus uses one primary resistance mechanism. An enzyme, called penicillin-binding protein 2a (PBP2a), is brought into this biosynthetic pathway to complete the cross-linking. PBP2a effectively discriminates against the ?-lactam antibiotics as potential inhibitors, and in favor of the peptidoglycan substrate. The basis for this discrimination is an allosteric site, distal from the active site, that when properly occupied concomitantly opens the gatekeeper residues within the active site and realigns the conformation of key residues to permit catalysis. We address the molecular basis of this regulation using crystallographic studies augmented by computational analyses. The crystal structures of three ?-lactams (oxacillin, cefepime, ceftazidime) complexes with PBP2a-each with the ?-lactam in the allosteric site-defined (with preceding PBP2a structures) as the "open" or "partially open" PBP2a states. A particular loop motion adjacent to the active site is identified as the driving force for the active-site conformational change that accompanies active-site opening. Correlation of this loop motion to effector binding at the allosteric site, in order to identify the signaling pathway, was accomplished computationally in reference to the known "closed" apo-PBP2a X-ray crystal structure state. This correlation enabled the computational simulation of the structures coinciding with initial peptidoglycan substrate binding to PBP2a, acyl enzyme formation, and acyl transfer to a second peptidoglycan substrate to attain cross-linking. These studies offer important insights into the structural bases for allosteric site-to-active site communication and for ?-lactam mimicry of the peptidoglycan substrates, as foundational to the mechanistic understanding of emerging PBP2a resistance mutations.

Dataset Information

Proteomics and Docking Study Targeting Penicillin-Binding Protein and Penicillin-Binding Protein2a of Methicillin-Resistant Staphylococcus aureus Strain SO-1977 Isolated from Sudan.

Publications

Proteomics and Docking Study Targeting Penicillin-Binding Protein and Penicillin-Binding Protein2a of Methicillin-Resistant <i>Staphylococcus aureus</i> Strain SO-1977 Isolated from Sudan.

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