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Catalytic Site Atlas

CSA LITERATURE entry for 1jdw

E.C. nameglycine amidinotransferase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1jdwThere are 21 Homologs
CSA Entries With UniProtID P50440
CSA Entries With EC Number
PDBe Entry 1jdw
PDBSum Entry 1jdw
MACiE Entry M0018

Literature Report

IntroductionGlycine amidinotransferase, also known as L-arginine:glycine amidinotransferase (AT) catalyses the committed step in creatine biosynthesis. The enzyme does this by forming guanidinoacetic acid, the immediate precursor of creatine. Creatine and its phosphorylated form play an essential role in the energy metabolism of muscle and nerve tissues, acting as a dynamic reservoir of high-energy phosphate which buffers the rapid fluctuations of the ATP/ADP ratio during muscle and nerve action.
There are two isoforms; a mitochondrial and a cytoplasmic form. The mitochondrial form is found in the intermembrane space, probably attached to the outer side of the inner membrane.
MechansimThe reaction comprises of two steps, both involving nucleophilic attack. The first step starts by the addition of the carbon atom of the guanidino group of L-Arg to the thiol group of Cys407 of the enzyme, and donation of the thiol proton to the L-Arg substrate. Hydrogen bonds and salt linkage of the guanidino nitrogens to Asp170 and Asp305 enhance the electrophilicity of the guanidino-carbon atom, and a potential hydrogen bond of the epsilon-imino nitrogen to His303 supports proton transfer to this atom. Subsequently the bond between the epsilon-imino group and the amidino-carbon atom is broken to generate L-Orn. The second step starts with a proton transfer from the positively charged Gly substrate to His303 and a nucleophilic attack of the lone electron pair of the Gly nitrogen atom at the carbon atom of the bound amidino group. This is followed by the formation of a tetrahedral adduct and its collapse by cleavage of the amidino-carbon-sulfur bond to generate guanidinoacetic acid.

Catalytic Sites for 1jdw

Literature References

Shirai H
A novel superfamily of enzymes that catalyze the modification of guanidino groups.
Trends Biochem Sci 2001 26 465-468
PubMed: 11504612
Humm A
Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.
EMBO J 1997 16 3373-3385
PubMed: 9218780