1woj: Difference between revisions

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Crystal structure of human phosphodiesterase

OverviewOverview

2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP), a member of the 2H phosphoesterase superfamily, is firmly bound to brain white matter and found mainly in the central nervous system of vertebrates, and it catalyzes the hydrolysis of 2',3'-cyclic nucleotide to produce 2'-nucleotide. Recent studies on CNP-knockout mice have revealed that the absence of CNP causes axonal swelling and neuronal degeneration. Here, the crystal structure of the catalytic fragment (CF) of human CNP (hCNP-CF) is solved at 1.8A resolution. It is an alpha+beta type structure consisting of three alpha-helices and nine beta-strands. The structural core of the molecule is comprised of two topologically equivalent three-stranded antiparallel beta-sheets that are related by a pseudo 2-fold symmetry. Each beta-sheet contains an H-X-T-X motif, which is strictly conserved among members of the 2H phosphoesterase superfamily. The phosphate ion is bound to the side-chains of His and Thr from each of the two motifs. Structural comparison of hCNP-CF with plant 1,2-cyclic nucleotide phosphodiesterase (CPDase) and bacterial 2'-5' RNA ligase reveals that the H-X-T-X motifs are structurally conserved among these enzymes, but the surface properties of the active site are quite different among the enzymes, reflecting the differences in their substrates. On the basis of the present crystal structure of the hCNP-CF/phosphate complex, the available structure of the CPDase/cyclic-nucleotide analogue complex, and the recent functional studies of rat CNP-CF, we propose a possible substrate-binding mode and catalytic mechanism of CNP, which employs the nucleophilic water molecule activated by His310. The proposed mechanism is basically equivalent to the second step of the well-accepted reaction mechanism of RNase A. Since the overall structure of hCNP-CF differs considerably from that of RNase A, it is likely that the similar active sites with two catalytic histidine residues in these enzymes arose through convergent evolution.

About this StructureAbout this Structure

1WOJ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as 2',3'-cyclic-nucleotide 3'-phosphodiesterase, with EC number 3.1.4.37 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase., Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT, J Mol Biol. 2005 Feb 25;346(3):789-800. Epub 2005 Jan 12. PMID:15713463

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 '''Crystal structure of human phosphodiesterase'''<br />
 ==Overview==
-',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP), a member of the 2H, phosphoesterase superfamily, is firmly bound to brain white matter and, found mainly in the central nervous system of vertebrates, and it, catalyzes the hydrolysis of 2',3'-cyclic nucleotide to produce, 2'-nucleotide. Recent studies on CNP-knockout mice have revealed that the, absence of CNP causes axonal swelling and neuronal degeneration. Here, the, crystal structure of the catalytic fragment (CF) of human CNP (hCNP-CF) is, solved at 1.8A resolution. It is an alpha+beta type structure consisting, of three alpha-helices and nine beta-strands. The structural core of the, molecule is comprised of two topologically equivalent three-stranded, antiparallel beta-sheets that are related by a pseudo 2-fold symmetry., Each beta-sheet contains an H-X-T-X motif, which is strictly conserved, among members of the 2H phosphoesterase superfamily. The phosphate ion is, bound to the side-chains of His and Thr from each of the two motifs., Structural comparison of hCNP-CF with plant 1'',2''-cyclic nucleotide, phosphodiesterase (CPDase) and bacterial 2'-5' RNA ligase reveals that the, H-X-T-X motifs are structurally conserved among these enzymes, but the, surface properties of the active site are quite different among the, enzymes, reflecting the differences in their substrates. On the basis of, the present crystal structure of the hCNP-CF/phosphate complex, the, available structure of the CPDase/cyclic-nucleotide analogue complex, and, the recent functional studies of rat CNP-CF, we propose a possible, substrate-binding mode and catalytic mechanism of CNP, which employs the, nucleophilic water molecule activated by His310. The proposed mechanism is, basically equivalent to the second step of the well-accepted reaction, mechanism of RNase A. Since the overall structure of hCNP-CF differs, considerably from that of RNase A, it is likely that the similar active, sites with two catalytic histidine residues in these enzymes arose through, convergent evolution.
+',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP), a member of the 2H phosphoesterase superfamily, is firmly bound to brain white matter and found mainly in the central nervous system of vertebrates, and it catalyzes the hydrolysis of 2',3'-cyclic nucleotide to produce 2'-nucleotide. Recent studies on CNP-knockout mice have revealed that the absence of CNP causes axonal swelling and neuronal degeneration. Here, the crystal structure of the catalytic fragment (CF) of human CNP (hCNP-CF) is solved at 1.8A resolution. It is an alpha+beta type structure consisting of three alpha-helices and nine beta-strands. The structural core of the molecule is comprised of two topologically equivalent three-stranded antiparallel beta-sheets that are related by a pseudo 2-fold symmetry. Each beta-sheet contains an H-X-T-X motif, which is strictly conserved among members of the 2H phosphoesterase superfamily. The phosphate ion is bound to the side-chains of His and Thr from each of the two motifs. Structural comparison of hCNP-CF with plant 1'',2''-cyclic nucleotide phosphodiesterase (CPDase) and bacterial 2'-5' RNA ligase reveals that the H-X-T-X motifs are structurally conserved among these enzymes, but the surface properties of the active site are quite different among the enzymes, reflecting the differences in their substrates. On the basis of the present crystal structure of the hCNP-CF/phosphate complex, the available structure of the CPDase/cyclic-nucleotide analogue complex, and the recent functional studies of rat CNP-CF, we propose a possible substrate-binding mode and catalytic mechanism of CNP, which employs the nucleophilic water molecule activated by His310. The proposed mechanism is basically equivalent to the second step of the well-accepted reaction mechanism of RNase A. Since the overall structure of hCNP-CF differs considerably from that of RNase A, it is likely that the similar active sites with two catalytic histidine residues in these enzymes arose through convergent evolution.
 ==About this Structure==
-WOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/2',3'-cyclic-nucleotide_3'-phosphodiesterase 2',3'-cyclic-nucleotide 3'-phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.37 3.1.4.37] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WOJ OCA].
+WOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/2',3'-cyclic-nucleotide_3'-phosphodiesterase 2',3'-cyclic-nucleotide 3'-phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.37 3.1.4.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WOJ OCA].
 ==Reference==
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 [[Category: Ichimiya, T.]]
 [[Category: Kurihara, T.]]
-[[Category: Nakamura, K.T.]]
+[[Category: Nakamura, K T.]]
 [[Category: Sakamoto, Y.]]
 [[Category: Tanaka, N.]]
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 [[Category: hydrolase]]
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