CYTH-like (also known as triphosphate tunnel metalloenzyme (TTM)-like) Phosphatases
CYTH-like superfamily enzymes hydrolyze triphosphate-containing substrates and require metal cations as cofactors. They have a unique active site located at the center of an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel). The name CYTH originated from the gene designation for bacterial class IV adenylyl cyclases (CyaB), and from thiamine triphosphatase. Class IV adenylate cyclases catalyze the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. Thiamine triphosphatase is a soluble cytosolic enzyme which converts thiamine triphosphate to thiamine diphosphate. This domain superfamily also contains RNA triphosphatases, membrane-associated polyphosphate polymerases, tripolyphosphatases, nucleoside triphosphatases, nucleoside tetraphosphatases and other proteins with unknown functions.
Comment:This active site includes the putative metal binding and triphosphate binding sites.
Structure:3BHD_A; Human ThTPase bound to a citric acid molecule and a sulfate ion, contacts determined at 4A.
Comment:For 3BHD_A, the citrate is positioned similarly to the triphosphate of ThTP, the sulfate ion is positioned similarly to the alpha-phosphate of the substrate.
Structure:3G3R_A; Saccharomyces cerevisiae PolyP Polymerase bound with Mn2+; contacts determined at 4.5A.
Structure:3G3R_A; Saccharomyces cerevisiae VTC4 polyP polymerase bound with a substrate analog (adenosine-5prime-[(beta,gamma)-imido] triphosphate) and Mn2+, contacts determined at 4.5A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",