2gf3: Difference between revisions
New page: left|200px<br /><applet load="2gf3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gf3, resolution 1.30Å" /> '''Structure of the com... |
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[[Image:2gf3.jpg|left|200px]]<br /><applet load="2gf3" size=" | [[Image:2gf3.jpg|left|200px]]<br /><applet load="2gf3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2gf3, resolution 1.30Å" /> | caption="2gf3, resolution 1.30Å" /> | ||
'''Structure of the complex of monomeric sarcosine with its substrate analogue inhibitor 2-fuoric acid at 1.3 A resolution.'''<br /> | '''Structure of the complex of monomeric sarcosine with its substrate analogue inhibitor 2-fuoric acid at 1.3 A resolution.'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Monomeric sarcosine oxidases (MSOXs) are among the simplest | BACKGROUND: Monomeric sarcosine oxidases (MSOXs) are among the simplest members of a recently recognized family of eukaryotic and prokaryotic enzymes that catalyze similar oxidative reactions with various secondary or tertiary amino acids and contain covalently bound flavins. Other members of this family include heterotetrameric sarcosine oxidase, N-methyltryptophan oxidase and pipecolate oxidase. Mammalian sarcosine dehydrogenase and dimethylglycine dehydrogenase may be more distantly related family members. RESULTS: The X-ray crystal structure of MSOX from Bacillus sp. B-0618, expressed in Escherichia coli, has been solved at 2.0 A resolution by multiwavelength anomalous dispersion (MAD) from crystals of the selenomethionine-substituted enzyme. Fourteen selenium sites, belonging to two MSOX molecules in the asymmetric unit, were used for MAD phasing and to define the local twofold symmetry axis for electron-density averaging. The structures of the native enzyme and of two enzyme-inhibitor complexes were also determined. CONCLUSIONS: MSOX is a two-domain protein with an overall topology most similar to that of D-amino acid oxidase, with which it shares 14% sequence identity. The flavin ring is located in a very basic environment, making contact with sidechains of arginine, lysine, histidine and the N-terminal end of a helix dipole. The flavin is covalently attached through an 8alpha-S-cysteinyl linkage to Cys315 of the catalytic domain. Covalent attachment is probably self-catalyzed through interactions with the positive sidechains and the helix dipole. Substrate binding is probably stabilized by hydrogen bonds between the substrate carboxylate and two basic sidechains, Arg52 and Lys348, located above the re face of the flavin ring. | ||
==About this Structure== | ==About this Structure== | ||
2GF3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_sp. Bacillus sp.] with CL, PO4, FAD, FOA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sarcosine_oxidase Sarcosine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.1 1.5.3.1] Full crystallographic information is available from [http:// | 2GF3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_sp. Bacillus sp.] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=FAD:'>FAD</scene>, <scene name='pdbligand=FOA:'>FOA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Sarcosine_oxidase Sarcosine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.1 1.5.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GF3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chen, Z.]] | [[Category: Chen, Z.]] | ||
[[Category: Jorns, M | [[Category: Jorns, M S.]] | ||
[[Category: Mathews, F | [[Category: Mathews, F S.]] | ||
[[Category: Trickey, P.]] | [[Category: Trickey, P.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: inhibitor 2-fuoric acid]] | [[Category: inhibitor 2-fuoric acid]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:31:02 2008'' | ||
Revision as of 18:31, 21 February 2008
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Structure of the complex of monomeric sarcosine with its substrate analogue inhibitor 2-fuoric acid at 1.3 A resolution.
OverviewOverview
BACKGROUND: Monomeric sarcosine oxidases (MSOXs) are among the simplest members of a recently recognized family of eukaryotic and prokaryotic enzymes that catalyze similar oxidative reactions with various secondary or tertiary amino acids and contain covalently bound flavins. Other members of this family include heterotetrameric sarcosine oxidase, N-methyltryptophan oxidase and pipecolate oxidase. Mammalian sarcosine dehydrogenase and dimethylglycine dehydrogenase may be more distantly related family members. RESULTS: The X-ray crystal structure of MSOX from Bacillus sp. B-0618, expressed in Escherichia coli, has been solved at 2.0 A resolution by multiwavelength anomalous dispersion (MAD) from crystals of the selenomethionine-substituted enzyme. Fourteen selenium sites, belonging to two MSOX molecules in the asymmetric unit, were used for MAD phasing and to define the local twofold symmetry axis for electron-density averaging. The structures of the native enzyme and of two enzyme-inhibitor complexes were also determined. CONCLUSIONS: MSOX is a two-domain protein with an overall topology most similar to that of D-amino acid oxidase, with which it shares 14% sequence identity. The flavin ring is located in a very basic environment, making contact with sidechains of arginine, lysine, histidine and the N-terminal end of a helix dipole. The flavin is covalently attached through an 8alpha-S-cysteinyl linkage to Cys315 of the catalytic domain. Covalent attachment is probably self-catalyzed through interactions with the positive sidechains and the helix dipole. Substrate binding is probably stabilized by hydrogen bonds between the substrate carboxylate and two basic sidechains, Arg52 and Lys348, located above the re face of the flavin ring.
About this StructureAbout this Structure
2GF3 is a Single protein structure of sequence from Bacillus sp. with , , , and as ligands. Active as Sarcosine oxidase, with EC number 1.5.3.1 Full crystallographic information is available from OCA.
ReferenceReference
Monomeric sarcosine oxidase: structure of a covalently flavinylated amine oxidizing enzyme., Trickey P, Wagner MA, Jorns MS, Mathews FS, Structure. 1999 Mar 15;7(3):331-45. PMID:10368302
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