Sandbox GGC8

5YPI Mechanism of NDM-1

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D The 5YPI structure of NDM-1 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 antibiotic family: (Carbapenems)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 2009.My paper" The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis" explores the mechanism reaction of New Delhi metallo-beta-lactamases using NMR and crystallography, the hydrolysis of three enzyme-intermediates are examined, EI1, EI2, and EP, The data suggested that the hydrolytic intermediates are protonated by a bulky water molecule incoming from the β-face. This research is important because it could help provide a design model for mechanism-based inhibitors. The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis Han Feng, Xuehui Liu, Sheng Wang, Joy Fleming, Da-Cheng Wang & Wei Liu == Function == Hydrolase == Disease == New Delhi metallo-beta-lactamase 1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. Structural highlights Secondary Structure This scene shows the different secondary structures color-coded. Alpha Helices,  Beta Strands ,  Loops , Turns. Composition This scene shows the Protein, solvent, and ligand sites color coded below. Protein Ligand Solvent Elements This scene shows the different elements color coded. C H O N P S Se Fe Chains This scene shows the 8 chains linked together. Zn Pairs This scene shows the 8 Zn pairs(one for each chain). elements-only This scene shows a view of the molecules without the secondary structures.

References

https://www.nature.com/articles/s41467-017-02339-w https://rdcu.be/MgiZ