Literature summary for 3.4.19.9 extracted from

Chuankhayan, P.; Kao, T.T.; Lin, C.C.; Guan, H.H.; Nakagawa, A.; Fu, T.F.; Chen, C.J.
Structural insights into the hydrolysis and polymorphism of methotrexate polyglutamate by zebrafish gamma-glutamyl hydrolase (2013), J. Med. Chem., 56, 7625-7635.

Crystallization (Commentary)

Crystallization (Comment)	Organism
wild-type and mutants C108A and H218N in complex with substrate methotrexate pentaglutamate and product methotrexate glutamate, to 1.9 to 2.4 A resolution. The side chain of residue Phe20 and the 6-methylpterin ring of methotrexate pentaglutamate invoke pi-pi interactions to promote distinct concerted conformational alterations involving about 90° rotations in the complexes with the C108A and H218N mutant proteins	Danio rerio

Crystallization (Comment)

Organism

wild-type and mutants C108A and H218N in complex with substrate methotrexate pentaglutamate and product methotrexate glutamate, to 1.9 to 2.4 A resolution. The side chain of residue Phe20 and the 6-methylpterin ring of methotrexate pentaglutamate invoke pi-pi interactions to promote distinct concerted conformational alterations involving about 90° rotations in the complexes with the C108A and H218N mutant proteins

Danio rerio

Protein Variants

Protein Variants	Comment	Organism
C108A	complete loss of hydrolytic activity	Danio rerio
F20A	about 40% decrease in hyrolytic activity	Danio rerio
F20A/C108A	complete loss of hydrolytic activity	Danio rerio
F20R	about 40% increase in hyrolytic activity	Danio rerio
F20R/C108A	complete loss of hydrolytic activity	Danio rerio
H218N	complete loss of hydrolytic activity. Residue His218 alone suffices to catalyze the hydrolysis of the gamma-glutamate bond in gamma-glutamyl hydrolase	Danio rerio

Organism

Organism	UniProt	Comment	Textmining
Danio rerio	Q6NY42	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
methotrexate pentaglutamate + H2O	-	Danio rerio	methotrexate glutamate + tetra-gamma-L-glutamate	-	?

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Release 2023.1 (January 2023)