EC Number   |
Reaction |
Reference |
|---|
   3.4.24.27 | preferential cleavage: -/-Leu > -/-Phe |
- |
- |
| 3.4.24.27 | preferential cleavage: -/-Leu > -/-Phe |
classical molecular dynamics simulation., and ab initio quantum mechanics/molecular mechanics, QM/MM, investigation of the Glu143-assisted water addition mechanism in thermolysin peptide hydrolysis. The mechanism consists of three distinct steps: (i) a Zn-bound water molecule is deprotonated by Glu143 and attacks the carbonyl bond of the substrate; (ii) Glu143 transfers the proton to the amide nitrogen atom; (iii) the nitrogen atom is protonated and the peptide bond is irreversibly broken. Transition state stabilization for nucleophilic attack is achieved by formation of a weak coordination bond between the substrate carbonyl oxygen atom and the Zn ion and of three strong hydrogen bonds between the substrate and protonated His231 and two solvent molecules, overview |
683701 |
| 3.4.24.27 | preferential cleavage: -/-Leu > -/-Phe |
substrate turnover is associated with hinge bending that leads to a closed conformation. Product release regenerates the open form, such that steady-state catalysis involves a continuous closing/opening cycle. Elements in the periphery of the two lobes are most mobile. These peripheral regions undergo quite pronounced structural changes during the catalytic cycle. In contrast, active site residues exhibit only a moderate degree of backbone flexibility, and the central zinc appears to be in a fairly rigid environment. The hydrogen/deuterium exchange behavior of catalytically active thermolysin is indistinguishable from that of the free enzyme |
696272 |
