1xva: Difference between revisions
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[[Image:1xva.gif|left|200px]]<br /><applet load="1xva" size=" | [[Image:1xva.gif|left|200px]]<br /><applet load="1xva" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1xva, resolution 2.2Å" /> | caption="1xva, resolution 2.2Å" /> | ||
'''METHYLTRANSFERASE'''<br /> | '''METHYLTRANSFERASE'''<br /> | ||
==Overview== | ==Overview== | ||
Glycine N-methyltransferase (GNMT) from rat liver is a tetrameric enzyme | Glycine N-methyltransferase (GNMT) from rat liver is a tetrameric enzyme with 292 amino acid residues in each identical subunit and catalyzes the S-adenosylmethionine (AdoMet) dependent methylation of glycine to form sarcosine. The crystal structure of GNMT complexed with AdoMet and acetate, a competitive inhibitor of glycine, has been determined at 2.2 A resolution. The subunit of GNMT forms a spherical shape with an extended N-terminal region which corks the entrance of active site of the adjacent subunit. The active site is located in the near center of the spherical subunit. As a result, the AdoMet and acetate in the active site are completely surrounded by amino acid residues. Careful examination of the structure reveals several characteristics of GNMT. (1) Although the structure of the AdoMet binding domain of the GNMT is very similar to those of other methyltransferases recently determined by X-ray diffraction method, an additional domain found only in GNMT encloses the active site to form a molecular basket, and consequently the structure of GNMT looks quite different from those of other methyltransferases. (2) This unique molecular structure can explain why GNMT can capture folate and polycyclic aromatic hydrocarbons. (3) The unique N-terminal conformation and the subunit structure can explain why GNMT exhibits positive cooperativity in binding AdoMet. From the structural features of GNMT, we propose that the enzyme might be able to capture yet unidentified molecules in the cytosol and thus participates in various biological processes including detoxification of polycyclic aromatic hydrocarbons. In the active site, acetate binds near the S-CH3 moiety of AdoMet. Simple modeling indicates that the amino group of the substrate glycine can be placed close to the methyl group of AdoMet within 3.0 A and form a hydrogen bond with the carboxyl group of Glu15 of the adjacent subunit. On the basis of the ternary complex structure, the mechanism of the methyl transfer in GNMT has been proposed. | ||
==About this Structure== | ==About this Structure== | ||
1XVA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ACT and SAM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycine_N-methyltransferase Glycine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.20 2.1.1.20] Full crystallographic information is available from [http:// | 1XVA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=SAM:'>SAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycine_N-methyltransferase Glycine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.20 2.1.1.20] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XVA OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: methyltransferase]] | [[Category: methyltransferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:59:02 2008'' | ||
Revision as of 16:59, 21 February 2008
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METHYLTRANSFERASE
OverviewOverview
Glycine N-methyltransferase (GNMT) from rat liver is a tetrameric enzyme with 292 amino acid residues in each identical subunit and catalyzes the S-adenosylmethionine (AdoMet) dependent methylation of glycine to form sarcosine. The crystal structure of GNMT complexed with AdoMet and acetate, a competitive inhibitor of glycine, has been determined at 2.2 A resolution. The subunit of GNMT forms a spherical shape with an extended N-terminal region which corks the entrance of active site of the adjacent subunit. The active site is located in the near center of the spherical subunit. As a result, the AdoMet and acetate in the active site are completely surrounded by amino acid residues. Careful examination of the structure reveals several characteristics of GNMT. (1) Although the structure of the AdoMet binding domain of the GNMT is very similar to those of other methyltransferases recently determined by X-ray diffraction method, an additional domain found only in GNMT encloses the active site to form a molecular basket, and consequently the structure of GNMT looks quite different from those of other methyltransferases. (2) This unique molecular structure can explain why GNMT can capture folate and polycyclic aromatic hydrocarbons. (3) The unique N-terminal conformation and the subunit structure can explain why GNMT exhibits positive cooperativity in binding AdoMet. From the structural features of GNMT, we propose that the enzyme might be able to capture yet unidentified molecules in the cytosol and thus participates in various biological processes including detoxification of polycyclic aromatic hydrocarbons. In the active site, acetate binds near the S-CH3 moiety of AdoMet. Simple modeling indicates that the amino group of the substrate glycine can be placed close to the methyl group of AdoMet within 3.0 A and form a hydrogen bond with the carboxyl group of Glu15 of the adjacent subunit. On the basis of the ternary complex structure, the mechanism of the methyl transfer in GNMT has been proposed.
About this StructureAbout this Structure
1XVA is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Glycine N-methyltransferase, with EC number 2.1.1.20 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of glycine N-methyltransferase from rat liver., Fu Z, Hu Y, Konishi K, Takata Y, Ogawa H, Gomi T, Fujioka M, Takusagawa F, Biochemistry. 1996 Sep 17;35(37):11985-93. PMID:8810903
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