1bj4 | pdb_00001bj4

RECOMBINANT SERINE HYDROXYMETHYLTRANSFERASE (HUMAN)

spinqualitylabelsall models 1bj4, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1bj4 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PLP Activity: Glycine hydroxymethyltransferase, with EC number 2.1.2.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GLYC_HUMAN] Interconversion of serine and glycine. 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 BACKGROUND: Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme found in all prokaryotes and eukaryotes. As an enzyme of the thymidylate synthase metabolic cycle, SHMT catalyses the retro-aldol cleavage of serine to glycine, with the resulting hydroxymethyl group being transferred to tetrahydrofolate to form 5, 10-methylene-tetrahydrofolate. The latter is the major source of one-carbon units in metabolism. Elevated SHMT activity has been shown to be coupled to the increased demand for DNA synthesis in rapidly proliferating cells, particularly tumour cells. Consequently, the central role of SHMT in nucleotide biosynthesis makes it an attractive target for cancer chemotherapy. RESULTS: We have solved the crystal structure of human cytosolic SHMT by multiple isomorphous replacement to 2.65 A resolution. The monomer has a fold typical for alpha class pyridoxal 5'-phosphate (PLP) dependent enzymes. The tetramer association is best described as a 'dimer of dimers' where residues from both subunits of one 'tight' dimer contribute to the active site. CONCLUSIONS: The crystal structure shows the evolutionary relationship between SHMT and other alpha class PLP-dependent enzymes, as the fold is highly conserved. Many of the results of site-directed mutagenesis studies can easily be rationalised or re-interpreted in light of the structure presented here. For example, His 151 is not the catalytic base, contrary to the findings of others. A mechanism for the cleavage of serine to glycine and formaldehyde is proposed. The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy.,Renwick SB, Snell K, Baumann U Structure. 1998 Sep 15;6(9):1105-16. PMID:9753690 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine hydroxymethyltransferase

Proteopedia Page Contributors and Editors (what is this?)

OCA