5tkc

Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex

spinqualitylabelsall models 5tkc, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tkc is a 1 chain structure with sequence from Toxoplasma gondii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.779Å Ligands: 13P, G3H, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALF1_TOXGO Plays a key role in glycolysis by catalyzing the cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (PubMed:19380114, PubMed:25284756, PubMed:28972169). Forms a bridge between cell surface adhesins and the actin cytoskeleton (PubMed:12718875, PubMed:19380114). Required for parasite invasion of host cells (PubMed:19380114). Publication Abstract from PubMed Fructose-1,6-bisphosphate (FBP) aldolase, a glycolytic enzyme, catalyzes the reversible and stereospecific aldol addition of dihydroxyacetone-P (DHAP) and D-glyceraldehyde-3-P (D-G3P) by an unresolved mechanism. To afford insight into the molecular determinants of FBP aldolase stereospecificity during aldol addition, a key ternary complex formed by DHAP and D-G3P, comprising 2 % of the equilibrium population at physiological pH, was cryotrapped in the active site of Toxoplasma gondii aldolase (TgALD) crystals to high resolution. The growth of TgALD crystals in acidic conditions enabled trapping of the ternary complex as a dominant population. The obligate 3(S)-4(R) stereochemistry at the nascent C3-C4 bond of FBP requires a si-face attack by the covalent DHAP nucleophile on the D-G3P aldehyde si-face in the active site. The cis-isomer of the D-G3P aldehyde, representing the dominant population trapped in the ternary complex, would lead to re-face attack on the aldehyde and yield tagatose 1,6-bisphosphate, a competitive inhibitor of the enzyme. We propose that unhindered rotational isomerization by the D-G3P aldehyde moiety in the ternary complex generates the active trans-isomer competent for carbonyl bond activation by active-site residues, thereby enabling si-face attack by the DHAP enamine. C-C bond formation by the cis-isomer is suppressed by hydrogen-bonding of the cis-aldehyde carbonyl with the DHAP enamine phosphate dianion through a tetrahedrally coordinated water molecule. The active site geometry further suppresses C-C bond formation with the L-G3P enantiomer of D-G3P. Understanding C-C formation is of fundamental importance in biological reactions and has considerable relevance to biosynthetic reactions in organic chemistry. Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases.,Heron PW, Sygusch J J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures

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