View source for 1wsv

[[Image:1wsv.gif|left|200px]]<br /><applet load="1wsv" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1wsv, resolution 2.60&Aring;" />
'''Crystal Structure of Human T-protein of Glycine Cleavage System'''<br />

==Overview==
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.

==Disease==
Known disease associated with this structure: Glycine encephalopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=238310 238310]]

==About this Structure==
1WSV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=THH:'>THH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aminomethyltransferase Aminomethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.10 2.1.2.10] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSV OCA]. 

==Reference==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16051266 16051266]
[[Category: Aminomethyltransferase]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Fujiwara, K.]]
[[Category: Hosaka, H.]]
[[Category: Motokawa, Y.]]
[[Category: Nakagawa, A.]]
[[Category: Okamura-Ikeda, K.]]
[[Category: Taniguchi, H.]]
[[Category: Toma, S.]]
[[Category: Yamashita, E.]]
[[Category: Yoshimura, M.]]
[[Category: SO4]]
[[Category: THH]]
[[Category: aminomethyl transferase]]
[[Category: glycine-cleavage sytem]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:47:44 2008''