1wsr

<table><tr><td colspan='2'>[[1wsr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1WSR FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wsv|1wsv]]</div></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GCST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1wsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wsr OCA], [http://pdbe.org/1wsr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wsr RCSB], [http://www.ebi.ac.uk/pdbsum/1wsr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wsr ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/GCST_HUMAN GCST_HUMAN]] Defects in AMT are a cause of non-ketotic hyperglycinemia (NKH) [MIM:[http://omim.org/entry/605899 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.<ref>PMID:8005589</ref> <ref>PMID:9600239</ref> <ref>PMID:9621520</ref> <ref>PMID:10873393</ref> <ref>PMID:11286506</ref>

[[http://www.uniprot.org/uniprot/GCST_HUMAN GCST_HUMAN]] The glycine cleavage system catalyzes the degradation of glycine.

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== 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<ref>PMID:16051266</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1wsr" style="background-color:#fffaf0;"></div>

[[Category: Aminomethyltransferase]]

[[Category: Human]]

[[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: Transferase]]