'''Crystal structure of human phosphodiesterase'''
===Crystal structure of human phosphodiesterase===
==Overview==
<!--
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.
The line below this paragraph, {{ABSTRACT_PUBMED_15713463}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15713463 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_15713463}}
==About this Structure==
==About this Structure==
Line 29:
Line 33:
[[Category: Tanaka, N.]]
[[Category: Tanaka, N.]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:56:53 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:42:02 2008''
Revision as of 10:42, 28 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
1WOJ is a Single protein structure of sequence from Homo sapiens. 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
