This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
Sandbox 124
From Proteopedia
(Difference between revisions)
(Removing all content from page) |
|||
| Line 1: | Line 1: | ||
| - | =='''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 | ||
| - | North Shore-LIJ School of Medicine, Hempstead, NY 11549, USA | ||
| - | |||
| - | ---- | ||
| - | ---- | ||
| - | <Structure load='4dki' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
| - | ==='''Introduction'''=== | ||
| - | Transpeptidases ('''TP'''), also known as penicillin-binding proteins ('''PBP'''), | ||
| - | catalyze the cross-linking of peptidoglycan polymers during bacterial cell wall | ||
| - | synthesis. The natural transpeptidase substrate is the D-Ala-D-Ala | ||
| - | peptidoglycan side chain terminus. Beta-lactam ('''β-lactam''') antibiotics, which | ||
| - | include penicillins, cephalosporins and carbapenems, bind and irreversibly | ||
| - | inhibit transpeptidases by mimicking the D-Ala-D-Ala substrate, resulting in | ||
| - | the inhibition of cell wall synthesis and ultimately bacterial cell growth. | ||
| - | Overuse and misuse of β-lactams has led to the generation of methicillin resistant | ||
| - | Staphylococcus aureus ('''MRSA''') isolates that have acquired an | ||
| - | alternative transpeptidase, PBP2a, which is neither bound nor inhibited by β- | ||
| - | lactams. MRSA isolates are resistant to all β-lactams, can be hospital- or | ||
| - | community-acquired, and are often the cause of significant morbidity and | ||
| - | mortality. Furthermore, they are often only susceptible to “last resort | ||
| - | antibiotics”, such as vancomycin. Recently, two cephalosporins - ceftobiprole | ||
| - | and ceftaroline - that bind and inhibit PBP2a have been developed. The | ||
| - | Hostos-Lincoln Academy Students Modeling A Research Topic (SMART) | ||
| - | Team generated a model of the PBP2a/ceftobiprole complex (PDB [[4dki]]) | ||
| - | using 3D printing technology to illustrate the mechanism of action of | ||
| - | ceftobiprole. Supported by a grant from the Camille and Henry Dreyfus Foundation. | ||
