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This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439.


Penicillin binding protein/lactivicin (inhibitor) (2jch)[1]

by Tyler Carpenter, Samuel Pierce, Hyunjoon Choi, Anton El Khoury and Tiankai Zhang

Student Projects for UMass Chemistry 423 Spring 2016 <StructureSection load='2jch' size='350' side='right' caption='Saves cells from dying since the appearance of life (2jch)' scene=>

Introduction

Outline: 1) Why is it important? Penicillin-binding proteins are essential for cell wall biogenesis. General info about bacterial cell wall biogenesis. Also, how bacteria mutate in order to avoid binding to beta-lactam. 2) Ligands, in particular phenoxyacetyl lactivicin. Also, how PBP binds lactivicin. Sample green scene: Penicillin-binding protein has four ligands, one of which is the electron-deficient olefin ligand or EDO

Overall Structure

The secondary structures of PBP have certain affects on ligands TextToBeDisplayed Ligand has oxyanion hole to further binding potential. How does this help?


Binding Interactions

Penicillin binding protein binds to beta-lactam antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan. The beta-lactam amide bond is ruptured to form a covalent bond with the catalytic serine at the binding protein's active site.

Additional Features

1)role in antibiotics and resistance the role of PBPsmetabolic pathways and enzymes are unique to bacteria in its synthesis is a very good target for drugs of selective toxicity

2)different PBPs and how they are classified into diverse categories found as both membrane-bound and cytoplasmic proteins

3)work as enzyme to catalyze synthesis of peptidoglycan


Quiz Question 1

Question related to PBP evolution and developing resistance to ß-lactams, likely related to active site mutations. Shows the conserved residues of Penicillin Binding Protein from most conserved to most variable. 


See Also

Credits

Introduction - Anton El Khoury

Overall Structure - Tyler Carpenter

Drug Binding Site - Hyunjoon Choi

Additional Features - Tiankai Zhang

Quiz Question 1 - Samuel Pierce

References

  1. ↑ Macheboeuf P, Fischer DS, Brown T Jr, Zervosen A, Luxen A, Joris B, Dessen A, Schofield CJ. Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins. Nat Chem Biol. 2007 Sep;3(9):565-9. Epub 2007 Aug 5. PMID:17676039 doi:10.1038/nchembio.2007.21