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1wsv
From Proteopedia
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| - | [[Image:1wsv.gif|left|200px]] | + | [[Image:1wsv.gif|left|200px]] |
| - | + | ||
| - | '''Crystal Structure of Human T-protein of Glycine Cleavage System''' | + | {{Structure |
| + | |PDB= 1wsv |SIZE=350|CAPTION= <scene name='initialview01'>1wsv</scene>, resolution 2.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=THH:N-[4-({[(6S)-2-AMINO-4-HYDROXY-5-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID'>THH</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= GCST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of Human T-protein of Glycine Cleavage System''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1WSV is a [ | + | 1WSV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSV OCA]. |
==Reference== | ==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:// | + | 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://www.ncbi.nlm.nih.gov/pubmed/16051266 16051266] |
[[Category: Aminomethyltransferase]] | [[Category: Aminomethyltransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: glycine-cleavage sytem]] | [[Category: glycine-cleavage sytem]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:01:04 2008'' |
Revision as of 13:01, 20 March 2008
| |||||||
| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | GCST (Homo sapiens) | ||||||
| Activity: | Aminomethyltransferase, with EC number 2.1.2.10 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human T-protein of Glycine Cleavage System
Contents |
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:[238310]
About this Structure
1WSV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from 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:16051266
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