Sandbox Reserved 988
From Proteopedia
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== History == | == History == | ||
| - | Many medical textbooks recount Alexander Flemming’s serendipitous observation of the antibacterial action of Penicillium mold in 1928. While not the first to note the inhibitory effect, Flemming became the first to seriously push the scientific community to research the isolation of the active compound, which he named penicillin. Eventually these efforts paid off, and in 1940, Sir Ernst Boris Chain published a method of isolating and purifying penicillin and tested its clinical effectiveness in mice. | + | Many medical textbooks recount Alexander Flemming’s serendipitous observation of the antibacterial action of Penicillium mold in 1928. While not the first to note the inhibitory effect, Flemming became the first to seriously push the scientific community to research the isolation of the active compound, which he named penicillin. Eventually these efforts paid off, and in 1940, Sir Ernst Boris Chain published a method of isolating and purifying penicillin and tested its clinical effectiveness in mice. Later that year, he identified the first β-lactamase in Escherichia coli. While interesting, this discovery was not considered clinically relevant until β-lactamase enzymes were isolated from clinical samples of gram positive bacteria by Dr. William M. M. Kirby. |
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
Revision as of 16:20, 14 December 2015
| This Sandbox is Reserved from 20/01/2015, through 30/04/2016 for use in the course "CHM 463" taught by Mary Karpen at the Grand Valley State University. This reservation includes Sandbox Reserved 987 through Sandbox Reserved 996. |
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This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Background
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 of bacteria and function in cross-linking to form the peptidoglycan layer. PBPs have a conserved, 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.[3]
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.[4]
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 [5] 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.
History
Many medical textbooks recount Alexander Flemming’s serendipitous observation of the antibacterial action of Penicillium mold in 1928. While not the first to note the inhibitory effect, Flemming became the first to seriously push the scientific community to research the isolation of the active compound, which he named penicillin. Eventually these efforts paid off, and in 1940, Sir Ernst Boris Chain published a method of isolating and purifying penicillin and tested its clinical effectiveness in mice. Later that year, he identified the first β-lactamase in Escherichia coli. While interesting, this discovery was not considered clinically relevant until β-lactamase enzymes were isolated from clinical samples of gram positive bacteria by Dr. William M. M. Kirby.
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Disease
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ "Peptidoglycan cell wall." The University of Warwick. n.d. Web. 25 Jan 15
- ↑ Beta Lactam Antibiotics, 2011. Antimicrobial Resistance Learning Site. Michigan State University Department of Pharmacology. 16 Sept, 2014.
- ↑ Powers, Rachel, Hollister C. Swanson, Magdalena A. Taracila, Nicholas W. Florek, Chiara Romagnoli, Emilia Caselli, Fabio Prati, Robert A. Bonomo, and Bradley J. Wallar. Biochemical and Structural Analysis of Inhibitors Targeting the ADC-7 Cephalosporinase of Acinetobacter baumannii. Biochemistry, 2014, 53 (48), 7670-7679.
