1wsv: Difference between revisions
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|PDB= 1wsv |SIZE=350|CAPTION= <scene name='initialview01'>1wsv</scene>, resolution 2.60Å | |PDB= 1wsv |SIZE=350|CAPTION= <scene name='initialview01'>1wsv</scene>, resolution 2.60Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <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] | |ACTIVITY= <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> | ||
|GENE= GCST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= GCST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1wsr|1WSR]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wsv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wsv OCA], [http://www.ebi.ac.uk/pdbsum/1wsv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wsv RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Yamashita, E.]] | [[Category: Yamashita, E.]] | ||
[[Category: Yoshimura, M.]] | [[Category: Yoshimura, M.]] | ||
[[Category: aminomethyl transferase]] | [[Category: aminomethyl transferase]] | ||
[[Category: glycine-cleavage sytem]] | [[Category: glycine-cleavage sytem]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:40:31 2008'' | ||
