Entry M0288    glutaryl-7-aminocephalosporanic-acid acylase

Next Step

Step 01

A water molecule acts as a proton carrier in the deprotonation of the Ser170A side chain hydroxyl by the N terminal amine group.

GIF of Reaction Step M0288.stg01

Comment: The presence of low barrier hydrogen bonds between Ser170, His193, Glu525 and the conserved water molecule facilitates proton transfer by lowering the activation energy associated with each step. The interactions also orientate the nucleophilic Ser170 towards the substrate's glutaryl group in the next step.
The protonation state of the N terminus is mediated through hydrogen bonding interactions between the amine nitrogen, His193A and Glu525A which work in partnership as a catalytic dyad. This dyad, present between His193A, Glu525A and Ser170A, is similar to that seen for serine proteases, although the hydrogen bond to Ser170A involves the terminal amine group, rather than the side chain hydroxyl [1,2].


Proton Transfer

Mechanism Components

Bond Formation
Bond Cleavage
Proton Relay

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Val140A Main Chain Amide spectator Hydrogen Bond Donor
Asn314A Side Chain spectator Hydrogen Bond Donor
Glu525A Side Chain spectator Hydrogen Bond Acceptor
Increase Basicity
His193A Side Chain spectator Hydrogen Bond Donor
Hydrogen Bond Acceptor
Increase Basicity
Ser170A Side Chain reactant Hydrogen Bond Donor
Proton Donor
Ser170A Main Chain N Terminus reactant Proton Acceptor
Hydrogen Bond Acceptor

Reactive Centre

Bonds Formed Bonds Cleaved Bonds Changed in Order Atom Types Involved

View similar reactions in MACiE.