1wsv

Crystal Structure of Human T-protein of Glycine Cleavage SystemCrystal Structure of Human T-protein of Glycine Cleavage System

Structural highlights 1wsv is a 2 chain structure with sequence from Homo sapiens. 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: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GCST_HUMAN Defects in AMT are a cause of non-ketotic hyperglycinemia (NKH) [MIM:605899; also known as glycine encephalopathy (GCE). NKH is an autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. Function GCST_HUMAN The glycine cleavage system catalyzes the degradation of 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 T-protein, a component of the glycine cleavage system, catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. Several mutations in the human T-protein gene cause non-ketotic hyperglycinemia. To gain insights into the effect of disease-causing mutations and the catalytic mechanism at the molecular level, crystal structures of human T-protein in free form and that bound to 5-methyltetrahydrofolate (5-CH3-H4folate) have been determined at 2.0 A and 2.6 A resolution, respectively. The overall structure consists of three domains arranged in a cloverleaf-like structure with the central cavity, where 5-CH3-H4folate is bound in a kinked shape with the pteridine group deeply buried into the hydrophobic pocket and the glutamyl group pointed to the C-terminal side surface. Most of the disease-related residues cluster around the cavity, forming extensive hydrogen bonding networks. These hydrogen bonding networks are employed in holding not only the folate-binding space but also the positions and the orientations of alpha-helix G and the following loop in the middle region, which seems to play a pivotal role in the T-protein catalysis. Structural and mutational analyses demonstrated that Arg292 interacts through water molecules with the folate polyglutamate tail, and that the invariant Asp101, located close to the N10 group of 5-CH3-H4folate, might play a key role in the initiation of the catalysis by increasing the nucleophilic character of the N10 atom of the folate substrate for the nucleophilic attack on the aminomethyl lipoate intermediate. A clever mechanism of recruiting the aminomethyl lipoate arm to the reaction site seems to function as a way of avoiding the release of toxic formaldehyde. Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia.,Okamura-Ikeda K, Hosaka H, Yoshimura M, Yamashita E, Toma S, Nakagawa A, Fujiwara K, Motokawa Y, Taniguchi H J Mol Biol. 2005 Sep 2;351(5):1146-59. PMID:16051266 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminomethyltransferase 3D structures

spinqualitylabelsall models 1wsv, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image