1l4h: Difference between revisions

Revision as of 14:41, 21 February 2008

Crystal Structure of CobT complexed with indole and nicotinate mononucleotide

OverviewOverview

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.

About this StructureAbout this Structure

1L4H is a Single protein structure of sequence from Salmonella enterica with and as ligands. Active as Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase, with EC number 2.4.2.21 Full crystallographic information is available from OCA.

ReferenceReference

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

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-[[Image:1l4h.gif|left|200px]]<br /><applet load="1l4h" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1l4h.gif|left|200px]]<br /><applet load="1l4h" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1l4h, resolution 2.10&Aring;" />
 '''Crystal Structure of CobT complexed with indole and nicotinate mononucleotide'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-L4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with IND and NCN 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L4H OCA].
+L4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with <scene name='pdbligand=IND:'>IND</scene> and <scene name='pdbligand=NCN:'>NCN</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=1L4H OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Salmonella enterica]]
 [[Category: Single protein]]
-[[Category: Cheong, C.G.]]
+[[Category: Cheong, C G.]]
 [[Category: Escalante-Semerena, J.]]
 [[Category: Rayment, I.]]
@@ Line 26: / Line 26: @@
 [[Category: phosphoribosyltransferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:15:05 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:13 2008''