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Entry M0175    3.4.23.16    HIV-1 retropepsin

Previous Step

Step 02

Asp25B deprotonates the alcohol group of the intermediate, initiating an elimination that cleaves the peptide bond. The N-terminal product then deprotonates Asp25A.

Rate Determining Step

GIF of Reaction Step M0175.stg02


Comment: A hydrated bond is a flexible structure with a low energy barrier for an anti-Gauche C-N dihedral rotation. The optimisation of the binding of the entire substrate drives the hydrated peptide bound to the Gauche conformation [3]. Solvent isotope effects are consistent with the reaction proceeding by the rate-limiting step of dissociation of the enzyme-bound amide-hydrate intermediate. Kinetic studies also support that the cleavage of the C-N bond is the major contributor to Kcat [4].



Mechanisms

Proton Transfer
Bimolecular Elimination

Mechanism Components

Bond Formation
Bond Order Change
Bond Cleavage
Intermediate Collapse
Intermediate Terminated
Overall Product Formed
Enzyme Regenerated

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Asp25A Side Chain reactant Hydrogen Bond Donor
Proton Donor
Hydrogen Bond Acceptor
Gly27A Main Chain Amide spectator Hydrogen Bond Donor
Electrostatic Stabiliser
Asp25B Side Chain reactant Hydrogen Bond Acceptor
Proton Acceptor
Gly27B Main Chain Amide spectator Hydrogen Bond Donor

Reactive Centre

Bonds Formed Bonds Cleaved Bonds Changed in Order Atom Types Involved
N-H
O-H
C-N
O-H
O-H
The C-O bond changes from a single to double bond
C
H
N
O

View similar reactions in MACiE.


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