1d0s
From Proteopedia
(New page: 200px<br /><applet load="1d0s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d0s, resolution 1.9Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1d0s.gif|left|200px]]<br /><applet load="1d0s" size=" | + | [[Image:1d0s.gif|left|200px]]<br /><applet load="1d0s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d0s, resolution 1.9Å" /> | caption="1d0s, resolution 1.9Å" /> | ||
'''CRYSTAL STRUCTURE OF NICOTINATE MONONUCLEOTIDE : 5,6-DIMETHYLBENZIMIDAZOLE PHOSPHORIBOSYLTRANSFERASE (COBT) FROM SALMONELLA TYPHIMURIUM COMPLEXED WITH 5, 6-DIMETHYLBENZIMIDAZOLE'''<br /> | '''CRYSTAL STRUCTURE OF NICOTINATE MONONUCLEOTIDE : 5,6-DIMETHYLBENZIMIDAZOLE PHOSPHORIBOSYLTRANSFERASE (COBT) FROM SALMONELLA TYPHIMURIUM COMPLEXED WITH 5, 6-DIMETHYLBENZIMIDAZOLE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nicotinate mononucleotide:5,6-dimethylbenzimidazole | + | Nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium plays a central role in the synthesis of alpha-ribazole, which is a key component of the lower ligand of cobalamin. Two X-ray structures of CobT are reported here at 1.9 A resolution. First, a complex of CobT with 5,6-dimethylbenzimidazole, and second, a complex of CobT with its reaction products, nicotinate and alpha-ribazole-5'-phosphate. CobT was cocrystallized with 5,6-dimethylbenzimidazole (DMB) in the space group P2(1)2(1)2 with unit cell dimensions of a = 72.1 A, b = 90.2 A, and c = 47.5 A and one protomer per asymmetric unit. Subsequently, the crystals containing DMB were soaked in nicotinate mononucleotide whereupon the physiological reaction occurred in the crystal lattice to yield nicotinate and alpha-ribazole-5'-phosphate. These studies show that CobT is a dimer where each subunit consists of two domains. The large domain is dominated by a parallel six-stranded beta-sheet with connecting alpha-helices that exhibit the topology of a Rossmann fold. The small domain is made from components of the N- and C-terminal sections of the polypeptide chain and contains a three-helix bundle. The fold of CobT is unrelated to the type I and II phosphoribosylpyrophosphate dependent transferases and does not appear to be related to any other protein whose structure is known. The enzyme active site is located in a large cavity formed by the loops at the C-terminal ends of the beta-strands and the small domain of the neighboring subunit. DMB binds in a hydrophobic pocket created in part by the neighboring small domain. This is consistent with the broad specificity of this enzyme for aromatic substrates [Trzebiatowski, J. R., Escalante-Semerena (1997) J. Biol. Chem. 272, 17662-17667]. The binding site for DMB suggests that Glu317 is the catalytic base required for the reaction. The remainder of the cavity binds the nicotinate and ribose-5'-phosphate moieties, which are nestled within the loops at the ends of the beta-strands. Interestingly, the orientation of the substrate and products are opposite from that expected for a Rossmann fold. |
==About this Structure== | ==About this Structure== | ||
| - | 1D0S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with PO4 and DMD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide--dimethylbenzimidazole_phosphoribosyltransferase Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.21 2.4.2.21] Full crystallographic information is available from [http:// | + | 1D0S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=DMD:'>DMD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide--dimethylbenzimidazole_phosphoribosyltransferase Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.21 2.4.2.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D0S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Salmonella typhimurium]] | [[Category: Salmonella typhimurium]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cheong, C | + | [[Category: Cheong, C G.]] |
| - | [[Category: Escalante-Semerena, J | + | [[Category: Escalante-Semerena, J C.]] |
[[Category: Rayment, I.]] | [[Category: Rayment, I.]] | ||
[[Category: DMD]] | [[Category: DMD]] | ||
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[[Category: phosphoribosyl transferase]] | [[Category: phosphoribosyl transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:11:45 2008'' |
Revision as of 10:11, 21 February 2008
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CRYSTAL STRUCTURE OF NICOTINATE MONONUCLEOTIDE : 5,6-DIMETHYLBENZIMIDAZOLE PHOSPHORIBOSYLTRANSFERASE (COBT) FROM SALMONELLA TYPHIMURIUM COMPLEXED WITH 5, 6-DIMETHYLBENZIMIDAZOLE
Overview
Nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium plays a central role in the synthesis of alpha-ribazole, which is a key component of the lower ligand of cobalamin. Two X-ray structures of CobT are reported here at 1.9 A resolution. First, a complex of CobT with 5,6-dimethylbenzimidazole, and second, a complex of CobT with its reaction products, nicotinate and alpha-ribazole-5'-phosphate. CobT was cocrystallized with 5,6-dimethylbenzimidazole (DMB) in the space group P2(1)2(1)2 with unit cell dimensions of a = 72.1 A, b = 90.2 A, and c = 47.5 A and one protomer per asymmetric unit. Subsequently, the crystals containing DMB were soaked in nicotinate mononucleotide whereupon the physiological reaction occurred in the crystal lattice to yield nicotinate and alpha-ribazole-5'-phosphate. These studies show that CobT is a dimer where each subunit consists of two domains. The large domain is dominated by a parallel six-stranded beta-sheet with connecting alpha-helices that exhibit the topology of a Rossmann fold. The small domain is made from components of the N- and C-terminal sections of the polypeptide chain and contains a three-helix bundle. The fold of CobT is unrelated to the type I and II phosphoribosylpyrophosphate dependent transferases and does not appear to be related to any other protein whose structure is known. The enzyme active site is located in a large cavity formed by the loops at the C-terminal ends of the beta-strands and the small domain of the neighboring subunit. DMB binds in a hydrophobic pocket created in part by the neighboring small domain. This is consistent with the broad specificity of this enzyme for aromatic substrates [Trzebiatowski, J. R., Escalante-Semerena (1997) J. Biol. Chem. 272, 17662-17667]. The binding site for DMB suggests that Glu317 is the catalytic base required for the reaction. The remainder of the cavity binds the nicotinate and ribose-5'-phosphate moieties, which are nestled within the loops at the ends of the beta-strands. Interestingly, the orientation of the substrate and products are opposite from that expected for a Rossmann fold.
About this Structure
1D0S is a Single protein structure of sequence from Salmonella typhimurium with and as ligands. Active as Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase, with EC number 2.4.2.21 Full crystallographic information is available from OCA.
Reference
The three-dimensional structures of nicotinate mononucleotide:5,6- dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium complexed with 5,6-dimethybenzimidazole and its reaction products determined to 1.9 A resolution., Cheong CG, Escalante-Semerena JC, Rayment I, Biochemistry. 1999 Dec 7;38(49):16125-35. PMID:10587435
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