Sandbox Reserved 992: Difference between revisions
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[[Image:Beta-lactam.jpg|200px|thumb|left|A [http://en.m.wikipedia.org/wiki/Beta-lactam_antibiotic β-lactam antibiotic] ([http://en.m.wikipedia.org/wiki/Penicillin Penicillin])]]Clinically, [http://en.m.wikipedia.org/wiki/Beta-lactam_antibiotic β-lactam antibiotics], characterized by their central chemical structure, are utilized to combat bacterial infections by targeting [http://proteopedia.org/wiki/index.php/Penicillin-binding_protein penicillin-binding proteins] (PBPs), also known as [http://en.m.wikipedia.org/wiki/DD-transpeptidase transpeptidases]. PBPs are enzymes that are located in the cell membrane of bacteria and function in cross-linking to form the [http://en.m.wikipedia.org/wiki/Peptidoglycan peptidoglycan] layer. PBPs have a conserved [http://en.m.wikipedia.org/wiki/Deprotonation deprotonated] serine which executes [http://en.m.wikipedia.org/wiki/Nucleophile nucleophilic] attack on the [http://en.m.wikipedia.org/wiki/Carbonyl 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:Beta-lactam.jpg|200px|thumb|left|A [http://en.m.wikipedia.org/wiki/Beta-lactam_antibiotic β-lactam antibiotic] ([http://en.m.wikipedia.org/wiki/Penicillin Penicillin])]]Clinically, [http://en.m.wikipedia.org/wiki/Beta-lactam_antibiotic β-lactam antibiotics], characterized by their central chemical structure, are utilized to combat bacterial infections by targeting [http://proteopedia.org/wiki/index.php/Penicillin-binding_protein penicillin-binding proteins] (PBPs), also known as [http://en.m.wikipedia.org/wiki/DD-transpeptidase transpeptidases]. PBPs are enzymes that are located in the cell membrane of bacteria and function in cross-linking to form the [http://en.m.wikipedia.org/wiki/Peptidoglycan peptidoglycan] layer. PBPs have a conserved [http://en.m.wikipedia.org/wiki/Deprotonation deprotonated] serine which executes [http://en.m.wikipedia.org/wiki/Nucleophile nucleophilic] attack on the [http://en.m.wikipedia.org/wiki/Carbonyl 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 | [[Image:Peptidoglycan_cross_linking.png|500px|thumb|right|Peptidoglycan with PBP Cross-linking Mechanism]] | ||
The β-lactam ring covalently attaches to PBPs, [http://en.m.wikipedia.org/wiki/Enzyme_inhibitor 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 [http://en.m.wikipedia.org/wiki/Autolysis_(biology) autolysis].<ref name="MSUDP 2014"> | The β-lactam ring covalently attaches to PBPs, [http://en.m.wikipedia.org/wiki/Enzyme_inhibitor 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 [http://en.m.wikipedia.org/wiki/Autolysis_(biology) autolysis].<ref name="MSUDP 2014"> | ||
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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 [http://en.m.wikipedia.org/wiki/Acetylation deacylation], rendering it incapable of inhibiting the PBPs and ultimately, allowing cross-linking to occur for adequate cell wall formation. | 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 [http://en.m.wikipedia.org/wiki/Acetylation deacylation], rendering it incapable of inhibiting the PBPs and ultimately, allowing cross-linking to occur for adequate cell wall formation. | ||
[[Image:Beta-lactam inhibition.png|400px|thumb| | [[Image:Beta-lactam inhibition.png|400px|thumb|right|Image showing mechanism performed by β-lactam antibiotic within PBP [http://en.m.wikipedia.org/wiki/Active_site active site].]] | ||
== Class C Mechanism == | == Class C Mechanism == | ||