Sandbox Reserved 988: Difference between revisions

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{{Sandbox_gvsu_chm463}}

==Your Heading Here (maybe something like 'Structure')==

~~<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>~~

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 <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Background ==

[[Image:Beta-lactam.jpg|200px|thumb|right|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 four-membered cyclic amide, are utilized to combat various bacterial infections. This antibiotic class targets [http://proteopedia.org/wiki/index.php/Penicillin-binding_protein penicillin-binding proteins] (PBPs), also known as [http://en.m.wikipedia.org/wiki/DD-transpeptidase transpeptidase enzymes]. PBPs are enzymes that catalyze [http://en.wikipedia.org/wiki/Cross-link cross-linking] between strands of the [http://en.m.wikipedia.org/wiki/Peptidoglycan peptidoglycan] layer of the bacterial cell wall. <ref>"Peptidoglycan cell wall." The University of Warwick. n.d. Web. 25 Jan 15</ref> This cross-linking process strengthens the cell wall and enables the bacteria to resist [http://en.wikipedia.org/wiki/Osmotic_pressure osmotic pressure] from its external environment.

[[Image:Peptidoglycan_cross_linking.png|400px|thumb|left|Peptidoglycan with PBP Cross-linking Mechanism]]

β-lactam antibiotics covalently link to PBPs, [http://en.m.wikipedia.org/wiki/Enzyme_inhibitor inhibiting] them from cross-linking the peptidoglycan layer of the cell wall. The irreversible binding of the β-lactam antibiotic renders the PBP incapable of its catalytic function. This results in death of bacterial cells from osmotic instability or [http://en.m.wikipedia.org/wiki/Autolysis_(biology) autolysis].<ref name="MSUDP 2014">

Beta Lactam Antibiotics, 2011. Antimicrobial Resistance Learning Site. Michigan State University Department of Pharmacology. 16 Sept, 2014.

</ref>

One of the main causes of [http://en.wikipedia.org/wiki/Antimicrobial_resistance resistance] to β-lactam antibiotics is caused by β-lactamase enzymes. Chemically, β-lactamases and PBPs bind to β-lactam antibiotics in similar mechanisms. The catalytic serine of both enzymes performs a nucleophilic attack on to the carbonyl group in the β-lactam functional group of the antibiotic. Unlike PBPs, where the β-lactam antibiotics bind irreversibly, β-lactamases are able to undergo [http://en.m.wikipedia.org/wiki/Acetylation deacylation] in order to regenerate their active site. This process cleaves the β-lactam ring, ridding the β-lactam antibiotic of its antimicrobial activity. <ref>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.</ref> The cleaved β-lactam antibiotic is unable to inhibit PBPs, allowing cross-linking to occur for adequate cell wall formation.

== History ==

~~With myth-like reverence,~~ 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. ~~In the same~~ year, he identified the first β-lactamase in Escherichia coli. ~~They published their findings in a letter to the journal Nature titled, “An Enzyme from Bacteria able to Destroy Penicillin.”~~ 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

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.

== Structural Highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

~~== Function ==~~

== ~~Disease~~ ==

== Mechanism ==

~~== Relevance ==~~

Placeholder

== ~~Structural highlights~~ ==

== Inhibition ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Placeholder

</StructureSection>

== Disease ==

Placeholder

== References ==

Sandbox Reserved 988: Difference between revisions

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@@ Line 1: / Line 1: @@
 {{Sandbox_gvsu_chm463}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
 ==Your Heading Here (maybe something like 'Structure')==
-<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
 This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
 You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
+== Background ==
+[[Image:Beta-lactam.jpg|200px|thumb|right|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 four-membered cyclic amide, are utilized to combat various bacterial infections.  This antibiotic class targets [http://proteopedia.org/wiki/index.php/Penicillin-binding_protein penicillin-binding proteins] (PBPs), also known as [http://en.m.wikipedia.org/wiki/DD-transpeptidase transpeptidase enzymes]. PBPs are enzymes that catalyze [http://en.wikipedia.org/wiki/Cross-link cross-linking] between strands of the [http://en.m.wikipedia.org/wiki/Peptidoglycan peptidoglycan] layer of the bacterial cell wall. <ref>"Peptidoglycan cell wall." The University of Warwick. n.d. Web. 25 Jan 15</ref> This cross-linking process strengthens the cell wall and enables the bacteria to resist [http://en.wikipedia.org/wiki/Osmotic_pressure osmotic pressure] from its external environment.
+[[Image:Peptidoglycan_cross_linking.png|400px|thumb|left|Peptidoglycan with PBP Cross-linking Mechanism]]
+β-lactam antibiotics covalently link to PBPs, [http://en.m.wikipedia.org/wiki/Enzyme_inhibitor inhibiting] them from cross-linking the peptidoglycan layer of the cell wall. The irreversible binding of the β-lactam antibiotic renders the PBP incapable of its catalytic function. This results in death of bacterial cells from osmotic instability or [http://en.m.wikipedia.org/wiki/Autolysis_(biology) autolysis].<ref name="MSUDP 2014">
+Beta Lactam Antibiotics, 2011. Antimicrobial Resistance Learning Site. Michigan State University Department of Pharmacology. 16 Sept, 2014.
+</ref>
+One of the main causes of [http://en.wikipedia.org/wiki/Antimicrobial_resistance resistance] to β-lactam antibiotics is caused by β-lactamase enzymes. Chemically, β-lactamases and PBPs bind to β-lactam antibiotics in similar mechanisms. The catalytic serine of both enzymes performs a nucleophilic attack on to the carbonyl group in the β-lactam functional group of the antibiotic. Unlike PBPs, where the β-lactam antibiotics bind irreversibly, β-lactamases are able to undergo [http://en.m.wikipedia.org/wiki/Acetylation deacylation] in order to regenerate their active site.  This process cleaves the β-lactam ring, ridding the β-lactam antibiotic of its antimicrobial activity. <ref>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.</ref> The cleaved β-lactam antibiotic is unable to inhibit PBPs, allowing cross-linking to occur for adequate cell wall formation.
 == History ==
-With myth-like reverence, 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.  In the same year, he identified the first β-lactamase in Escherichia coli.  They published their findings in a letter to the journal Nature titled, “An Enzyme from Bacteria able to Destroy Penicillin.”  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
+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=''>
+== Structural Highlights ==
+This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
-== Function ==
-== Disease ==
+== Mechanism ==
-== Relevance ==
+Placeholder
-== Structural highlights ==
+== Inhibition ==
-This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
+Placeholder
 </StructureSection>
+== Disease ==
+Placeholder
 == References ==
 <references/>