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 ==Crystal Structure of CobT complexed with 2-amino-p-cresol and nicotinate mononucleotide==
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 == Publication Abstract from PubMed ==
-The evolution of biosynthetic pathways is difficult to reconstruct in hindsight; however, the structures of the enzymes that are involved may provide insight into their development. One enzyme in the cobalamin biosynthetic pathway that appears to have evolved from a protein with different function is L-threonine-O-3-phosphate decarboxylase (CobD) from Salmonella enterica, which is structurally similar to histidinol phosphate aminotransferase [Cheong, C. G., Bauer, C. B., Brushaber, K. R., Escalante-Semerena, J. C., and Rayment, I. (2002) Biochemistry 41, 4798-4808]. This enzyme is responsible for synthesizing (R)-1-amino-2-propanol phosphate which is the precursor for the linkage between the nucleotide loop and the corrin ring in cobalamin. To understand the relationship between this decarboxylase and the aspartate aminotransferase family to which it belongs, the structures of CobD in its apo state, the apo state complexed with the substrate, and its product external aldimine complex have been determined at 1.46, 1.8, and 1.8 A resolution, respectively. These structures show that the enzyme steers the breakdown of the external aldimine toward decarboxylation instead of amino transfer by positioning the carboxylate moiety of the substrate out of the plane of the pyridoxal ring and by placing the alpha-hydrogen out of reach of the catalytic base provided by the lysine that forms the internal aldimine. It would appear that CobD evolved from a primordial PLP-dependent aminotransferase, where the selection was based on similarities between the stereochemical properties of the substrates rather than preservation of the fate of the external aldimine. These structures provide a sequence signature for distinguishing between L-threonine-O-3-phosphate decarboxylase and histidinol phosphate aminotransferases, many of which appear to have been misannotated.
+Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin. In earlier studies it proved difficult to obtain the structure of CobT bound to NaMN because it is hydrolyzed in the crystal lattice in the absence of the second substrate DMB. In an effort to map the reaction pathway of this enzyme, NaMN was captured in the active site with the substrate analogs 4,5-dimethyl-1,2-phenylenediamine, 4-methylcatechol, indole, 3,4-dimethylaniline, 2,5-dimethylaniline, 3,4-dimethylphenol, and 2-amino-p-cresol. Structures of these complexes reveal that they exclude water molecules responsible for the hydrolysis from the active site. These structures, together with the early complexes with alpha-ribazole-5'-phosphate and DMB, provide a complete description of the reaction pathway. They demonstrate that the nicotinate moiety and phosphate do not appear to move significantly between reactants and products but that the aromatic base and ribose moiety each move approximately 1.2 A toward each other in the transformation. This study also reveals that, like many other nucleotide binding proteins, coordination of DMB is accompanied by a disorder-order transition in a surface loop. The structure of apo-CobT is also reported.
-Structural studies of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica: the apo, substrate, and product-aldimine complexes.,Cheong CG, Escalante-Semerena JC, Rayment I Biochemistry. 2002 Jul 23;41(29):9079-89. PMID:12119022<ref>PMID:12119022</ref>
+Capture of a labile substrate by expulsion of water molecules from the active site of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica.,Cheong CG, Escalante-Semerena JC, Rayment I J Biol Chem. 2002 Oct 25;277(43):41120-7. Epub 2002 Jul 5. PMID:12101181<ref>PMID:12101181</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>