4jki

Crystal Structure of N10-Formyltetrahydrofolate Synthetase with ZD9331, Formylphosphate, and ADP

spinqualitylabelsall models 4jki, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jki is a 2 chain structure with sequence from Moorella thermoacetica ATCC 39073. This structure supersedes the now removed PDB entry 3sin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: ADP, SO4, XPO, ZD9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FTHS_MOOTA Publication Abstract from PubMed N(10) -formyltetrahydrofolate synthetase (FTHFS) is a folate enzyme that catalyzes the formylation of tetrahydrofolate (THF) in an ATP dependent manner. Structures of FTHFS from the thermophilic homoacetogen, Moorella thermoacetica, complexed with 1) a catalytic intermediate - formylphosphate (XPO) and product - ADP; 2) with an inhibitory substrate analog - folate; 3) with XPO and an inhibitory THF analog, ZD9331, were used to analyze the enzyme mechanism. Nucleophilic attack of the formate ion on the gamma phosphate of ATP leads to the formation of XPO and the first product ADP. A channel that leads to the putative formate binding pocket allows for the binding of ATP and formate in random order. Formate binding is due to interactions with the gamma-phosphate moiety of ATP and additionally to two hydrogen bonds from the backbone nitrogen of Ala276 and the side chain of Arg97. Upon ADP dissociation, XPO reorients and moves to the position previously occupied by the beta-phosphate of ATP. Conformational changes that occur due to the XPO presence apparently allow for the recruitment of the third substrate, THF, with its pterin moiety positioned between Phe384 and Trp412. This position overlaps with that of the bound nucleoside, which is consistent with a catalytic mechanism hypothesis that FTHFS works via a sequential ping-pong mechanism. More specifically, a random bi uni uni bi ping-pong ter ter mechanism is proposed. Additionally, the native structure originally reported at a 2.5 A resolution was redetermined at a 2.2 A resolution. Mechanism of N(10) -formyltetrahydrofolate synthetase derived from complexes with intermediates and inhibitors.,Celeste LR, Chai G, Bielak M, Minor W, Lovelace LL, Lebioda L Protein Sci. 2011 Nov 22. doi: 10.1002/pro.2005. PMID:22109967 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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