Sandbox 124: Difference between revisions
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=='''Physical Model of the Staphylococcus aureus Transpeptidase PBP2a in Complex with an Anti-Methicillin-Resistant Staphylococcus aureus Cephalosporin'''== | =='''Physical Model of the Staphylococcus aureus Transpeptidase PBP2a in Complex with an Anti-Methicillin-Resistant Staphylococcus aureus Cephalosporin'''== | ||
Fatima Assad1, Kavita Bhikhi1, Annie Briglall1, Diana Eusebio1, Edwin Flores1, Andrew Ramirez1, Hillary Ramirez1, Tashina Valentin1, Mohammed Zaman1, Joel L. Sussman2, Andrew L. Lovering3, Lars F. Westblade4, and Allison Granberry1 | |||
1Hostos-Lincoln Academy, 600 St. Ann’s Avenue, Bronx, NY 10455, USA; 2Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; 3School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK; 4Department of Pathology and Laboratory Medicine, Hofstra | 1Hostos-Lincoln Academy, 600 St. Ann’s Avenue, Bronx, NY 10455, USA; 2Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; 3School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK; 4Department of Pathology and Laboratory Medicine, Hofstra | ||
North Shore-LIJ School of Medicine, Hempstead, NY 11549, USA | North Shore-LIJ School of Medicine, Hempstead, NY 11549, USA | ||
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==='''Introduction'''=== | ==='''Introduction'''=== | ||
Transpeptidases (TP), also known as penicillin-binding proteins (PBP), | Transpeptidases ('''TP'''), also known as penicillin-binding proteins ('''PBP'''), | ||
catalyze the cross-linking of peptidoglycan polymers during bacterial cell wall | catalyze the cross-linking of peptidoglycan polymers during bacterial cell wall | ||
synthesis. The natural transpeptidase substrate is the D-Ala-D-Ala | synthesis. The natural transpeptidase substrate is the D-Ala-D-Ala | ||
peptidoglycan side chain terminus. Beta-lactam (β-lactam) antibiotics, which | peptidoglycan side chain terminus. Beta-lactam ('''β-lactam''') antibiotics, which | ||
include penicillins, cephalosporins and carbapenems, bind and irreversibly | include penicillins, cephalosporins and carbapenems, bind and irreversibly | ||
inhibit transpeptidases by mimicking the D-Ala-D-Ala substrate, resulting in | inhibit transpeptidases by mimicking the D-Ala-D-Ala substrate, resulting in | ||
the inhibition of cell wall synthesis and ultimately bacterial cell growth. | the inhibition of cell wall synthesis and ultimately bacterial cell growth. | ||
Overuse and misuse of β-lactams has led to the generation of | Overuse and misuse of β-lactams has led to the generation of methicillin resistant | ||
Staphylococcus aureus (MRSA) isolates that have acquired an | Staphylococcus aureus ('''MRSA''') isolates that have acquired an | ||
alternative transpeptidase, PBP2a, which is neither bound nor inhibited by β- | alternative transpeptidase, PBP2a, which is neither bound nor inhibited by β- | ||
lactams. MRSA isolates are resistant to all β-lactams, can be hospital- or | lactams. MRSA isolates are resistant to all β-lactams, can be hospital- or | ||
