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== Function and Mechanism == | == Function and Mechanism == | ||
| - | [[Image:Beta-lactam.jpg|200px|thumb|left|A β-lactam antibiotic (Penicillin)]]Clinically, β-lactam antibiotics, characterized by their central chemical structure, are utilized to combat bacterial infections by targeting penicillin-binding proteins (PBPs), also known as transpeptidases. PBPs are enzymes that are located in the cell membrane and function in cross-linking to form the peptidoglycan layer. PBPs have a deprotonated serine which executes nucleophilic attack on the carbonyl carbon. The PBP is then covalently attached to one unit of peptidoglycan. The amino group of an alanine on a second unit of peptidoglycan then performs a second nucleophilic attack on the carbonyl carbon, resulting in two covalently cross-linked peptidoglycan units and the regeneration of the catalytic PBP.<ref>"Peptidoglycan cell wall." The University of Warwick. n.d. Web. 25 Jan 15< | + | [[Image:Beta-lactam.jpg|200px|thumb|left|A β-lactam antibiotic (Penicillin)]]Clinically, β-lactam antibiotics, characterized by their central chemical structure, are utilized to combat bacterial infections by targeting penicillin-binding proteins (PBPs), also known as transpeptidases. PBPs are enzymes that are located in the cell membrane and function in cross-linking to form the peptidoglycan layer. PBPs have a deprotonated serine which executes nucleophilic attack on the carbonyl carbon. The PBP is then covalently attached to one unit of peptidoglycan. The amino group of an alanine on a second unit of peptidoglycan then performs a second nucleophilic attack on the carbonyl carbon, resulting in two covalently cross-linked peptidoglycan units and the regeneration of the catalytic PBP.<ref>"Peptidoglycan cell wall." The University of Warwick. n.d. Web. 25 Jan 15</ref> |
[[Image:Peptidoglycan_cross_linking.png|500px|thumb|right|Peptidoglycan with PDB Cross-linking Mechanism]] | [[Image:Peptidoglycan_cross_linking.png|500px|thumb|right|Peptidoglycan with PDB Cross-linking Mechanism]] | ||
Revision as of 05:38, 25 February 2015
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Class C β-lactamases are a subcategory of β-lactamase enzymes. These enzymes are produced by some bacteria and result in their resistance to a variety of β-lactam antibiotics. β-lactam antibiotics are classified based on their chemical structure which contains a four membered, amide containing ring known as the β-lactam ring. Class C β-lactamases specifically target cephalosporin antibiotics and deactivate their antimicrobial activity by hydrolyzing the β-lactam ring.
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Function and Mechanism
The β-lactam ring covalently attaches to PBPs, inhibiting them from executing their role in properly synthesizing the cell wall peptidoglycan layer, via nucleophilic attack of the carbonyl carbon. The β-lactam cannot be removed and thus permanently renders the PBP incapable of its catalytic function in cross-linking. Ultimately, this results in death of bacterial cells from osmotic instability or autolysis.[2]
One of the main causes of resistance to β-lactam drugs is caused by β-lactamases. Chemically, β-lactamases bind to β-lactams the same way β-lactams bind to PBPs. However, the β-lactamases are then able to deactivate the antimicrobial activity of the β-lactams by cleaving the β-lactam bound in the active site through a molecular process called deacylation, rendering it incapable of inhibiting the PBPs and ultimately, allowing cross-linking to occur for adequate cell wall formation.
Class C Mechanism
There are four main classes of β-lactamase enzymes, A, B, C, and D. While these main classes all disable the antimicrobial activity of β-lactams by breaking open the β-lactam ring at the amide bond, each class has individually conserved residues that allow the enzyme to maintain catalytic function. Classes A, C and D are most similar by functioning via catalytic serine, while class B functions via catalytic zinc.[3]
