1h0p
From Proteopedia
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CYCLOPHILIN_5 FROM C. ELEGANS
Overview
The free-living nematode Caenorhabditis elegans expresses 18 cyclophilin, isoforms, eight of which are conserved single domain forms, comprising two, closely related secreted or type B forms (CYP-5 and CYP-6). Recombinant, CYP-5 has been purified, crystallised and the X-ray structure solved to a, resolution of 1.75A. The detailed molecular architecture most strongly, resembles the structure of human cyclophilin B with conserved changes in, loop structure and N and C-terminal extensions. Interestingly, the active, site pocket is occupied by a molecule of dithiothreitol though this has, little effect on the geometry of the active site which is similar to other, cyclophilin structures. The peptidyl-prolyl isomerase activity of CYP-5, has been characterised against the substrate, N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, and gives a k(cat)/K(m) value, of 3.6x10(6)M(-1)s(-1) that compares with a value of 6.3x10(6)M(-1)s(-1), for human cyclophilin B. The immunosuppressive drug cyclosporin A binds, and inhibits CYP-5 with an IC(50) value of 50nM, which is comparable to, the value of 84nM found for human cyclophilin B. CYP-6 has 67% sequence, identity with CYP-5 and a molecular model was built based on the CYP-5, crystal structure. The model shows that CYP-5 and CYP-6 are likely to have, very similar structures, but with a markedly increased number of negative, charges distributed around the surface of CYP-6. The spatial expression, patterns of the cyclophilin B isoforms were examined using transgenic, animals carrying a LacZ reporter fusion to these genes, and both cyp-5 and, cyp-6 are found to be expressed in an overlapping fashion in the nematode, gut. The temporal expression pattern of cyp-5 was further determined and, revealed a constitutive expression pattern, with highest abundance levels, being found in the embryo.
About this Structure
1H0P is a Single protein structure of sequence from Caenorhabditis elegans with DTT as ligand. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.
Reference
Structural and biological characterisation of the gut-associated cyclophilin B isoforms from Caenorhabditis elegans., Picken NC, Eschenlauer S, Taylor P, Page AP, Walkinshaw MD, J Mol Biol. 2002 Sep 6;322(1):15-25. PMID:12215411
Page seeded by OCA on Tue Nov 20 16:22:34 2007
