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Sandbox GGC8
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<StructureSection load='5YPI' size='340' side='right' caption='Caption for this structure' scene='/78/781194/5ypi-1/1'> | <StructureSection load='5YPI' size='340' side='right' caption='Caption for this structure' scene='/78/781194/5ypi-1/1'> | ||
The 5YPI structure contains 14,682 atoms, 14,184 bonds, 2729 groups, and 8 chains. | The 5YPI structure contains 14,682 atoms, 14,184 bonds, 2729 groups, and 8 chains. | ||
| - | New Delhi metallo-beta-lactamases (NDMs), pose a serious threat due to their extremely efficient mechanism of hydrolysis on beta-lactam antibiotics. These antibiotics target the penicillin-binding proteins in enzymes found anchored in the cell membrane, which are involved in the cross-linking of the bacterial cell wall. The beta-lactam ring binds to different penicillin-binding proteins making them unable to do cell wall synthesis which leads to death of the bacterial cell. The NDM-1 gene causes the bacterium to produce an enzyme that neutralizes even the strongest antibiotics family: (Carbapenems) imipenem is in that family and only used as last resort.The antibiotics strain that carries the NDM-1 gene are so dangerous because we have no way to combat them. | + | New Delhi metallo-beta-lactamases (NDMs), pose a serious threat due to their extremely efficient mechanism of hydrolysis on beta-lactam antibiotics. These antibiotics target the penicillin-binding proteins in enzymes found anchored in the cell membrane, which are involved in the cross-linking of the bacterial cell wall. The beta-lactam ring binds to different penicillin-binding proteins making them unable to do cell wall synthesis which leads to death of the bacterial cell. The NDM-1 gene causes the bacterium to produce an enzyme that neutralizes even the strongest antibiotics family: (Carbapenems) imipenem is in that family and only used as last resort.The antibiotics strain that carries the NDM-1 gene are so dangerous because we have no way to combat them. Metallo-beta-lactamases-mediated hydrolysis happens in two steps: cleavage of the amide bond and protonation of the generated intermediate .After the formation of a Michaels complex (ES), a water/hydroxide molecule residing between the two Zn(II) ions acts as a nucleophile to attack the carbonyl carbon (C7) and cleave the C–N bond next the intermediate is protonated, and an EP complex is tentatively formed before product release from the enzyme pocket, this was first detected in a Klebsiella pneumoniae case in India (hence the name)in 2008. |
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| + | == Function == Hydrolase | ||
== Disease == New Delhi metallo-beta-lactamase 1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. | == Disease == New Delhi metallo-beta-lactamase 1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. | ||
== Structural highlights == | == Structural highlights == | ||
Revision as of 15:29, 22 April 2018
5YPI Mechanism of NDM-1
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