1jha

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{{STRUCTURE_1jha| PDB=1jha | SCENE= }}
{{STRUCTURE_1jha| PDB=1jha | SCENE= }}
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'''Structural Investigation of the Biosynthesis of Alternative Lower Ligands for Cobamides by Nicotinate Mononucleotide:5,6-Dimethylbenzimidazole Phosphoribosyltransferase (CobT) from Salmonella enterica'''
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===Structural Investigation of the Biosynthesis of Alternative Lower Ligands for Cobamides by Nicotinate Mononucleotide:5,6-Dimethylbenzimidazole Phosphoribosyltransferase (CobT) from Salmonella enterica===
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==Overview==
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Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole, a key component of the lower ligand of cobalamin. Surprisingly, CobT can phosphoribosylate a wide range of aromatic substrates, giving rise to a wide variety of lower ligands in cobamides. To understand the molecular basis for this lack of substrate specificity, the x-ray structures of CobT complexed with adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, p-cresol, and phenol were determined. Furthermore, adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, and 2-hydroxypurine were observed to react with NaMN within the crystal lattice and undergo the phosphoribosyl transfer reaction to form product. Significantly, the stereochemistries of all products are identical to those found in vivo. Interestingly, p-cresol and phenol, which are the lower ligand in Sporomusa ovata, bound to CobT but did not react with NaMN. This study provides a structural explanation for how CobT can phosphoribosylate most of the commonly observed lower ligands found in cobamides with the exception of the phenolic lower ligands observed in S. ovata. This is accomplished with minor conformational changes in the side chains that constitute the 5,6-dimethylbenzimidazole binding site. These investigations are consistent with the implication that the nature of the lower ligand is controlled by metabolic factors rather by the specificity of the phosphoribosyltransferase.
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(as it appears on PubMed at http://www.pubmed.gov), where 11441022 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11441022}}
==About this Structure==
==About this Structure==
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[[Category: N1-alpha-phosphoribosyltransferase]]
[[Category: N1-alpha-phosphoribosyltransferase]]
[[Category: Nn:dbi prt]]
[[Category: Nn:dbi prt]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:13:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:14:36 2008''

Revision as of 17:14, 1 July 2008

Image:1jha.png

Template:STRUCTURE 1jha

Structural Investigation of the Biosynthesis of Alternative Lower Ligands for Cobamides by Nicotinate Mononucleotide:5,6-Dimethylbenzimidazole Phosphoribosyltransferase (CobT) from Salmonella enterica

Template:ABSTRACT PUBMED 11441022

About this Structure

1JHA is a Single protein structure of sequence from Salmonella enterica. Full crystallographic information is available from OCA.

Reference

Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica., Cheong CG, Escalante-Semerena JC, Rayment I, J Biol Chem. 2001 Oct 5;276(40):37612-20. Epub 2001 Jul 5. PMID:11441022

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