1yjs

K226Q Mutant Of Serine Hydroxymethyltransferase From B. Stearothermophilus, Complex With Glycine

spinqualitylabelsall models 1yjs, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1yjs is a 1 chain structure with sequence from Geobacillus stearothermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: GLY, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q7SIB6_GEOSE Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Also exhibits THF-independent aldolase activity toward beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol mechanism.[HAMAP-Rule:MF_00051] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Serine hydroxymethyltransferase (SHMT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme catalyzes the reversible conversion of l-Ser and tetrahydropteroylglutamate (H(4)PteGlu) to Gly and 5,10-methylene tetrahydropteroylglutamate (CH(2)-H(4)PteGlu). Biochemical and structural studies on this enzyme have implicated several residues in the catalytic mechanism, one of them being the active site lysine, which anchors PLP. It has been proposed that this residue is crucial for product expulsion. However, in other PLP-dependent enzymes, the corresponding residue has been implicated in the proton abstraction step of catalysis. In the present investigation, Lys-226 of Bacillus stearothermophilus SHMT (bsSHMT) was mutated to Met and Gln to evaluate the role of this residue in catalysis. The mutant enzymes contained 1 mol of PLP per mol of subunit suggesting that Schiff base formation with lysine is not essential for PLP binding. The 3D structure of the mutant enzymes revealed that PLP was bound at the active site in an orientation different from that of the wild-type enzyme. In the presence of substrate, the PLP ring was in an orientation superimposable with that of the external aldimine complex of wild-type enzyme. However, the mutant enzymes were inactive, and the kinetic analysis of the different steps of catalysis revealed that there was a drastic reduction in the rate of formation of the quinonoid intermediate. Analysis of these results along with the crystal structures suggested that K-226 is responsible for flipping of PLP from one orientation to another which is crucial for H(4)PteGlu-dependent Calpha-Cbeta bond cleavage of l-Ser. Role of Lys-226 in the catalytic mechanism of Bacillus stearothermophilus serine hydroxymethyltransferase--crystal structure and kinetic studies.,Bhavani S, Trivedi V, Jala VR, Subramanya HS, Kaul P, Prakash V, Appaji Rao N, Savithri HS Biochemistry. 2005 May 10;44(18):6929-37. PMID:15865438 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine hydroxymethyltransferase 3D structures

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