Invanz Sandbox
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
| - | Invanz 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 penicilling binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a trans-1-hydroxyethyl group that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The beta lactam ring 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>. Some crystal structures of Invanz that help to elucidate its mechanism of action include <scene name='74/746003/4qu3/1'>4QU3</scene>, <scene name='74/746003/3zgp/1'>3ZGP</scene>, <scene name='74/746003/3m6b/1'>3M6B</scene> , and <scene name='74/746003/3m6h/1'>3M6H</scene>. The 4QU3 structure shows the GES-2 Ertapenem Acyl-Enzyme Complex crystalized bound to ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. The 4QU3 complex illustrates that the acylation event between the GES-2 enzyme and the Ertapenem leads inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref> The 3ZGP complex shows the NMR structure of the catalytic domain from the ''Enterococcus faecium'' L,d-transpeptidase acylated by ertapenem. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''Mycobacterium tuberculosis''. This structure shows that ertapenem is successfully inhibited by ertepenem through acylation of the ltd <ref>PMID: 23574509</ref> The 3M6B crystal structure of the pre-isomerized ertapenem covalent adduct with the M. tuberculosis beta-lactamase and the 3M6H crystal structure of the post-isomerize ertapenem covalent adduct with ''M. tuberculosis'' beta-lactamase comes from a publication that characterized the stability of the acyl-enzyme complex of the ertapenem while working to inhibit this bacteria <ref>PMID: 23574509</ref>. | + | Invanz 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 penicilling binding proteins <ref>PMID: 25485972</ref>. Invanz has resistance to many beta-lactamases since it has a trans-1-hydroxyethyl group that confers resistance of the antibiotic to degradation by most beta-lactamases <ref>PMID: 15150178 </ref> <ref name="hammond">...</ref>. The beta lactam ring 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>. Some crystal structures of Invanz that help to elucidate its mechanism of action include <scene name='74/746003/4qu3/1'>4QU3</scene>, <scene name='74/746003/3zgp/1'>3ZGP</scene>, <scene name='74/746003/3m6b/1'>3M6B</scene> , and <scene name='74/746003/3m6h/1'>3M6H</scene>. The 4QU3 structure shows the GES-2 Ertapenem Acyl-Enzyme Complex crystalized bound to ''Pseudomonas aeruginosa''. GES-1, GES-2, and GES-3 are the Guina Extended Spectrum beta-lactamases that help bacteria resist attack of antibiotics <ref>PMID: 15225858</ref>. The 4QU3 complex illustrates that the acylation event between the GES-2 enzyme and the Ertapenem leads inactivation of the GES-2 beta-lactamase, thus making the Ertapenem and effective treatment against the bacteria <ref>PMID: 18922024</ref> The 3ZGP complex shows the NMR structure of the catalytic domain from the ''Enterococcus faecium'' L,d-transpeptidase acylated by ertapenem. PBPs vital for peptidoglycan synthesis are replaced by l,d-transpeptidases (ltds) in an ampicillin-resistant strain of ''E. faecium'' and in ''Mycobacterium tuberculosis''. This structure shows that ertapenem is successfully inhibited by ertepenem through acylation of the ltd <ref>PMID: 23574509</ref> The 3M6B crystal structure of the pre-isomerized ertapenem covalent adduct with the ''M. tuberculosis'' beta-lactamase and the 3M6H crystal structure of the post-isomerize ertapenem covalent adduct with ''M. tuberculosis'' beta-lactamase comes from a publication that characterized the stability of the acyl-enzyme complex of the ertapenem while working to inhibit this bacteria <ref>PMID: 23574509</ref>. |
Revision as of 00:31, 5 December 2016
Invanz (Ertapenem) is a 1-beta-methyl carbapenem antibiotic that is designed to treat multi drug resistant bacterial infections such as intra-abdominal infections, skin and skin suture infections, community-acquired pneumonia, complicated urinary tract infections including pyelonephritis, acute pelvic infections, and can be used as a prophylactic measure prior to colorectal surgery. Invanz is an injectable antibiotic that can be administered intramuscularly [1][2].
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