5A65: Crystal Structure Of Mouse Thiamine Triphosphatase In Complex With Thiamine Diphosphate, Orthophosphate And Magnesium Ions

Citation:
Abstract
Triphosphate 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.
PDB ID: 5A65Download
MMDB ID: 131512
PDB Deposition Date: 2015/6/24
Updated in MMDB: 2015/08
Experimental Method:
x-ray diffraction
Resolution: 1.98  Å
Source Organism:
Similar Structures:
Biological Unit for 5A65: monomeric; determined by author and by software (PISA)
Molecular Components in 5A65
Label Count Molecule
Protein (1 molecule)
1
Thiamine Triphosphatase(Gene symbol: Thtpa)
Molecule annotation
Chemicals (5 molecules)
1
2
2
1
3
1
4
1
* Click molecule labels to explore molecular sequence information.

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