Sandbox 124: Difference between revisions

No edit summary
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 14: Line 14:




'''Cell Wall Structure'''
==='''Cell Wall Structure'''===
The cell wall, which is composed of peptidoglycans, is crucial for maintaining  
The cell wall, which is composed of peptidoglycans, is crucial for maintaining  
the structural integrity of the bacterium.  Peptidoglycans consists of  
the structural integrity of the bacterium.  Peptidoglycans consists of  
Line 29: Line 29:


==='''Catalytic Mechanism of PBP2a'''===
==='''Catalytic Mechanism of PBP2a'''===
[[Image:Schematic TP 3steps.jpg|thumb|alt= Alt text| |550px]]
[[Image:Schematic TP 3steps.jpg|thumb|alt= Alt text|Figure 2. Schematic showing Catalytic Mechanism of PBP2a |550px]]
(a) The D-Ala-D-Ala side-chain substrate of the peptidoglycan accesses  
(a) The D-Ala-D-Ala side-chain substrate of the peptidoglycan accesses  
the active site of the PBP2a.
the active site of the PBP2a.
Line 43: Line 43:
The entire process takes 4 milliseconds.
The entire process takes 4 milliseconds.


==='''How do antibiotics work?'''===
==='''How Do Antibiotics Work?'''===
The β-lactam antibiotics inhibit bacterial growth by inhibiting PBPs and ultimately cell wall
The β-lactam antibiotics inhibit bacterial growth by inhibiting PBPs and ultimately cell wall
synthesis. Specifically, β-lactams are molecular mimics of D-Ala-D-Ala, which is the normal
synthesis. Specifically, β-lactams are molecular mimics of D-Ala-D-Ala, which is the normal
Line 49: Line 49:
inhibited by the β-lactam. As a result, the synthesis of the cell wall is inhibited which leads
inhibited by the β-lactam. As a result, the synthesis of the cell wall is inhibited which leads
to cell lysis.
to cell lysis.
[[Image:Structures on penicillin and b lactam.jpg|thumb|alt= Alt text|Figure 3. Mechanism of action of β-lactams. A. Structure of a β-lactam (penicillin) showing the amide, carboxyl, and β-lactam ring groups β-lactam ring groups. B. Structure of the D-Ala-D-Ala substrate. C. Overlay of the D-Ala-D-Ala substrate in red with penicillin demonstrating molecular mimicry.|550 px]]


==='''PBP2a and Ceftobiprole'''===
==='''PBP2a and Ceftobiprole'''===
Line 60: Line 62:
residues in PBP2a; specifically  
residues in PBP2a; specifically  
<scene name='37/372724/Tyr446_and_met641_label/2'>Tyr446 and Met641</scene>.
<scene name='37/372724/Tyr446_and_met641_label/2'>Tyr446 and Met641</scene>.
As a result of its <scene name='37/372724/R2_interaction/4'>tighter binding</scene> to PBP2a, <scene name='37/372724/Tyr446_and_met641_label/3'>ceftobiprole </scene>, shown as colors of the atom types ([[CPK]]), is able to more efficiently react with the serine active site residue and therefore inhibit the activity of PBP2a.
As a result of ceftobiprole <scene name='37/372724/R2_interaction/4'>tighter binding</scene> to PBP2a as highlighted in green , <scene name='37/372724/Ceftobiprole_in_cpk/1'>the medicine</scene>, shown as colors of the atom types ([[CPK]]), is able to more efficiently react with the serine active site residue and therefore inhibit the activity of PBP2a.

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Wayne Decatur, Student, Allison Granberry, Marisa L. VanBrakle