Invanz Sandbox: Difference between revisions

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== Structural highlights ==

<scene name='74/746003/Invanz_with_features/1'>Invanz</scene> is a carbapenem which is a beta-lactam antibiotic (contains a beta lactam ring) that has antimicrobial action via inhibition of cell wall synthesis. This class of antibiotics is known for its broad spectrum of activity, and its structure allows it to bind penicillin binding proteins (PBPs) to inhibit bacterial cell wall synthesis in a variety of bacterial types <ref>PMID: 17488146</ref><ref name="Invanz1">...</ref>. Antibiotic resistance to carbapenems largely results from ability of the bacterial species to secrete beta-lactamase enzymes that prevent the antimicrobial from accomplishing its job. Beta-lactamases work by attacking and cleaving the beta-lactam ring of antibiotics before the antibiotic reaches its target such as the penicillin binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a <scene name='74/746003/Invanz_with_features/1'>trans-1-hydroxyethyl group</scene> (shown in pink) that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The <scene name='74/746003/Invanz_with_features/1'>beta-lactam ring</scene> (shown in purple) is a four-membered, nitrogen-containing ring that binds to PBPs, thus making them unable to continue bacterial cell wall synthesis. PBPs are enzymes found in the cell membrane that aid in cross-linking of peptidoglycan during cell wall synthesis <ref>PMID: 18266856</ref>. By inactivating PBPs and inhibiting cell wall synthesis, bacterial cell death will occur since the bacterial cells will lyse due to osmotic pressure <ref>Page, M.L. The mechanisms of reactions of beta lactam antibiotics. Accounts of Chemical Research, 1984, 17(4), 144-151 DOI: 10.1021/ar00100a005</ref>. There are various crystal structures of Invanz that help to elucidate its mechanism of action and effectiveness against some species of bacteria that are able to resist inhibition by other classes of antibiotics. The <scene name='74/746003/4qu3/1'>GES-2 Ertapenem Acyl-Enzyme Complex</scene> is a crystallized structure of Invanz bound to the GES-2 beta-lactamase in ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help some bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. This crystal structure complex is important for illustrating the acylation event between the GES-2 enzyme and the Ertapenem. Acylation of the enzyme leads to inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref> The <scene name='74/746003/3zgp/1'>NMR structure of the catalytic domain from Enterococcus faecium l,d-transpeptidase acylated by ertapenem</scene> shows that Invanz is an effective treatment against bacteria such as ''E. faecium'' and ''Mycobacterium tuberculosis''. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''M. tuberculosis''. This structure shows that bacterial strains such as ''E. faecium'' and ''M. tuberculosis'' are successfully inhibited by ertepenem through acylation of the ltd <ref>PMID: 23574509</ref> The <scene name='74/746003/3m6b/1'>crystal structure of the pre-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> and the <scene name='74/746003/3m6h/1'>crystal structure of the post-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> are structures from a publication that determined carbapenems such as Invanz can inhibit a bacterium such as ''M. tuberculosis'' by acetylating and slowly de-acetylating the acyl-enzyme complex in order to inhibit the beta-lactamase and effectively inhibit bacterial cell wall synthesis <ref>PMID: 23574509</ref>.

<scene name='74/746003/Invanz_with_features/1'>Invanz</scene> is a carbapenem which is a beta-lactam antibiotic (contains a beta lactam ring) that has antimicrobial action via inhibition of cell wall synthesis. This class of antibiotics is known for its broad spectrum of activity, and its structure allows it to bind penicillin binding proteins (PBPs) to inhibit bacterial cell wall synthesis in a variety of bacterial types <ref>PMID: 17488146</ref><ref name="Invanz1">...</ref>. Antibiotic resistance to carbapenems largely results from ability of the bacterial species to secrete beta-lactamase enzymes that prevent the antimicrobial from accomplishing its job. Beta-lactamases work by attacking and cleaving the beta-lactam ring of antibiotics before the antibiotic reaches its target such as the penicillin binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a <scene name='74/746003/Invanz_with_features/1'>trans-1-hydroxyethyl group</scene> (shown in pink) that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The <scene name='74/746003/Invanz_with_features/1'>beta-lactam ring</scene> (shown in purple) is a four-membered, nitrogen-containing ring that binds to PBPs, thus making them unable to continue bacterial cell wall synthesis. PBPs are enzymes found in the cell membrane that aid in cross-linking of peptidoglycan during cell wall synthesis <ref>PMID: 18266856</ref>. By inactivating PBPs and inhibiting cell wall synthesis, bacterial cell death will occur since the bacterial cells will lyse due to osmotic pressure <ref>Page, M.L. The mechanisms of reactions of beta lactam antibiotics. Accounts of Chemical Research, 1984, 17(4), 144-151 DOI: 10.1021/ar00100a005</ref>. There are various crystal structures of Invanz that help to elucidate its mechanism of action and effectiveness against some species of bacteria that are able to resist inhibition by other classes of antibiotics. The <scene name='74/746003/4qu3/1'>GES-2 Ertapenem Acyl-Enzyme Complex</scene> is a crystallized structure of Invanz bound to the GES-2 beta-lactamase in ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help some bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. This crystal structure complex is important for illustrating the acylation event between the GES-2 enzyme and the Ertapenem. Acylation of the enzyme leads to inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref>. The <scene name='74/746003/3zgp/1'>NMR structure of the catalytic domain from Enterococcus faecium l,d-transpeptidase acylated by ertapenem</scene> shows that Invanz is an effective treatment against bacteria such as ''E. faecium'' and ''Mycobacterium tuberculosis''. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''M. tuberculosis''. This structure shows that bacterial strains such as ''E. faecium'' and ''M. tuberculosis'' are successfully inhibited by ertepenem through acylation of the ltd Specifically, the beta-lactam ring of the ertapenem acylates the nucleophilic serine that normally catalyzes the transpeptidation reaction during cross-linking of the bacterial cell wall. The acylation of the ltd leads to formation of a stable acyl enzyme complex which effectively inactivates the ltd from continuing cell wall synthesis <ref>PMID: 23574509</ref>. The <scene name='74/746003/3m6b/1'>crystal structure of the pre-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> and the <scene name='74/746003/3m6h/1'>crystal structure of the post-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> are structures from a publication that determined carbapenems such as Invanz can inhibit a bacterium such as ''M. tuberculosis'' by acetylating and slowly de-acetylating the acyl-enzyme complex in order to inhibit the beta-lactamase and effectively inhibit bacterial cell wall synthesis <ref>PMID: 23574509</ref>.

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Revision as of 15:20, 5 December 2016 view source Courtney Stout (talk \| contribs) 110 edits No edit summary ← Older edit		Latest revision as of 18:50, 5 December 2016 view source Courtney Stout (talk \| contribs) 110 edits No edit summary
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	== Structural highlights ==		== Structural highlights ==
	<scene name='74/746003/Invanz_with_features/1'>Invanz</scene> is a carbapenem which is a beta-lactam antibiotic (contains a beta lactam ring) that has antimicrobial action via inhibition of cell wall synthesis. This class of antibiotics is known for its broad spectrum of activity, and its structure allows it to bind penicillin binding proteins (PBPs) to inhibit bacterial cell wall synthesis in a variety of bacterial types <ref>PMID: 17488146</ref><ref name="Invanz1">...</ref>. Antibiotic resistance to carbapenems largely results from ability of the bacterial species to secrete beta-lactamase enzymes that prevent the antimicrobial from accomplishing its job. Beta-lactamases work by attacking and cleaving the beta-lactam ring of antibiotics before the antibiotic reaches its target such as the penicillin binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a <scene name='74/746003/Invanz_with_features/1'>trans-1-hydroxyethyl group</scene> (shown in pink) that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The <scene name='74/746003/Invanz_with_features/1'>beta-lactam ring</scene> (shown in purple) is a four-membered, nitrogen-containing ring that binds to PBPs, thus making them unable to continue bacterial cell wall synthesis. PBPs are enzymes found in the cell membrane that aid in cross-linking of peptidoglycan during cell wall synthesis <ref>PMID: 18266856</ref>. By inactivating PBPs and inhibiting cell wall synthesis, bacterial cell death will occur since the bacterial cells will lyse due to osmotic pressure <ref>Page, M.L. The mechanisms of reactions of beta lactam antibiotics. Accounts of Chemical Research, 1984, 17(4), 144-151 DOI: 10.1021/ar00100a005</ref>. There are various crystal structures of Invanz that help to elucidate its mechanism of action and effectiveness against some species of bacteria that are able to resist inhibition by other classes of antibiotics. The <scene name='74/746003/4qu3/1'>GES-2 Ertapenem Acyl-Enzyme Complex</scene> is a crystallized structure of Invanz bound to the GES-2 beta-lactamase in ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help some bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. This crystal structure complex is important for illustrating the acylation event between the GES-2 enzyme and the Ertapenem. Acylation of the enzyme leads to inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref> The <scene name='74/746003/3zgp/1'>NMR structure of the catalytic domain from Enterococcus faecium l,d-transpeptidase acylated by ertapenem</scene> shows that Invanz is an effective treatment against bacteria such as ''E. faecium'' and ''Mycobacterium tuberculosis''. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''M. tuberculosis''. This structure shows that bacterial strains such as ''E. faecium'' and ''M. tuberculosis'' are successfully inhibited by ertepenem through acylation of the ltd <ref>PMID: 23574509</ref> The <scene name='74/746003/3m6b/1'>crystal structure of the pre-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> and the <scene name='74/746003/3m6h/1'>crystal structure of the post-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> are structures from a publication that determined carbapenems such as Invanz can inhibit a bacterium such as ''M. tuberculosis'' by acetylating and slowly de-acetylating the acyl-enzyme complex in order to inhibit the beta-lactamase and effectively inhibit bacterial cell wall synthesis <ref>PMID: 23574509</ref>.		<scene name='74/746003/Invanz_with_features/1'>Invanz</scene> is a carbapenem which is a beta-lactam antibiotic (contains a beta lactam ring) that has antimicrobial action via inhibition of cell wall synthesis. This class of antibiotics is known for its broad spectrum of activity, and its structure allows it to bind penicillin binding proteins (PBPs) to inhibit bacterial cell wall synthesis in a variety of bacterial types <ref>PMID: 17488146</ref><ref name="Invanz1">...</ref>. Antibiotic resistance to carbapenems largely results from ability of the bacterial species to secrete beta-lactamase enzymes that prevent the antimicrobial from accomplishing its job. Beta-lactamases work by attacking and cleaving the beta-lactam ring of antibiotics before the antibiotic reaches its target such as the penicillin binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a <scene name='74/746003/Invanz_with_features/1'>trans-1-hydroxyethyl group</scene> (shown in pink) that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The <scene name='74/746003/Invanz_with_features/1'>beta-lactam ring</scene> (shown in purple) is a four-membered, nitrogen-containing ring that binds to PBPs, thus making them unable to continue bacterial cell wall synthesis. PBPs are enzymes found in the cell membrane that aid in cross-linking of peptidoglycan during cell wall synthesis <ref>PMID: 18266856</ref>. By inactivating PBPs and inhibiting cell wall synthesis, bacterial cell death will occur since the bacterial cells will lyse due to osmotic pressure <ref>Page, M.L. The mechanisms of reactions of beta lactam antibiotics. Accounts of Chemical Research, 1984, 17(4), 144-151 DOI: 10.1021/ar00100a005</ref>. There are various crystal structures of Invanz that help to elucidate its mechanism of action and effectiveness against some species of bacteria that are able to resist inhibition by other classes of antibiotics. The <scene name='74/746003/4qu3/1'>GES-2 Ertapenem Acyl-Enzyme Complex</scene> is a crystallized structure of Invanz bound to the GES-2 beta-lactamase in ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help some bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. This crystal structure complex is important for illustrating the acylation event between the GES-2 enzyme and the Ertapenem. Acylation of the enzyme leads to inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref>. The <scene name='74/746003/3zgp/1'>NMR structure of the catalytic domain from Enterococcus faecium l,d-transpeptidase acylated by ertapenem</scene> shows that Invanz is an effective treatment against bacteria such as ''E. faecium'' and ''Mycobacterium tuberculosis''. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''M. tuberculosis''. This structure shows that bacterial strains such as ''E. faecium'' and ''M. tuberculosis'' are successfully inhibited by ertepenem through acylation of the ltd Specifically, the beta-lactam ring of the ertapenem acylates the nucleophilic serine that normally catalyzes the transpeptidation reaction during cross-linking of the bacterial cell wall. The acylation of the ltd leads to formation of a stable acyl enzyme complex which effectively inactivates the ltd from continuing cell wall synthesis <ref>PMID: 23574509</ref>. The <scene name='74/746003/3m6b/1'>crystal structure of the pre-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> and the <scene name='74/746003/3m6h/1'>crystal structure of the post-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase </scene> are structures from a publication that determined carbapenems such as Invanz can inhibit a bacterium such as ''M. tuberculosis'' by acetylating and slowly de-acetylating the acyl-enzyme complex in order to inhibit the beta-lactamase and effectively inhibit bacterial cell wall synthesis <ref>PMID: 23574509</ref>.