5a66
Crystal structure of AtTTM3 in complex with tripolyphosphate and manganese ion (form A)
Structural highlights
FunctionTTM3_ARATH Involved in the hydrolysis of the beta-gamma-phosphoanhydride linkage of triphosphate-containing substrates (inorganic or nucleoside-linked). Catalyzes the hydrolysis of inorganic triphosphate (PPPi), however it does not display significant activity towards long-chain polyphosphates. The existence of PPPi in living cells is still unclear, and PPPase activity might be the ancestral function of CYTH domain. It also has gamma-phosphatase activity on NTP substrates, but no adenylate cyclase or RNA triphosphatase activity.[1] Publication Abstract from PubMedTriphosphate tunnel metalloenzymes (TTMs) are present in all kingdoms of life and catalyze diverse enzymatic reactions such as mRNA capping, the cyclization of adenosine triphosphate, the hydrolysis of thiamine triphosphate and the synthesis and breakdown of inorganic polyphosphates. TTMs have an unusual tunnel domain fold that harbors substrate- and metal co-factor binding sites. It is presently poorly understood how TTMs specifically sense different triphosphate-containing substrates and how catalysis occurs in the tunnel center. Here we describe substrate-bound structures of inorganic polyphosphatases from Arabidopsis and E. coli, which reveal an unorthodox yet conserved mode of triphosphate and metal co-factor binding. We identify two metal binding sites in these enzymes, with one co-factor involved in substrate coordination and the other in catalysis. Structural comparisons with a substrate- and product-bound mammalian thiamine triphosphatase, and with previously reported structures of mRNA capping enzymes, adenylate cyclases and polyphosphate polymerases, suggest that directionality of substrate binding defines TTM catalytic activity. Our work provides insight into the evolution and functional diversification of an ancient enzyme family. Structural Determinants for Substrate Binding and Catalysis in Triphosphate Tunnel Metalloenzymes.,Martinez J, Truffault V, Hothorn M J Biol Chem. 2015 Jul 28. pii: jbc.M115.674473. PMID:26221030[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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