1dza
From Proteopedia
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| , resolution 1.65Å | |||||||
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| Ligands: | |||||||
| Gene: | PM7 (Homo sapiens) | ||||||
| Activity: | Pancreatic ribonuclease, with EC number 3.1.27.5 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
3-D STRUCTURE OF A HP-RNASE
Overview
We have determined the crystal structure of a human pancreatic ribonuclease or RNase 1 variant at 1.65 A resolution. Five residues in the N-terminal region were substituted by the corresponding amino acids of the bovine seminal RNase. In addition, a Pro to Ser mutation was present at position 50. The substitution of part of the N terminus has been critical both in improving the expression of this enzyme as a recombinant protein and in achieving its crystallisation. The determination of the crystal structure revealed the characteristic RNase fold including a V-shaped beta-sheet and three alpha-helices. It differs from its bovine RNase orthologue mainly in the loop regions. The active-site cleft shows a similar architecture to that of its bovine counterpart, with the essential residues occupying equivalent positions. In the present structure, however, His119 is displaced as it is in the structure of RNase A at high pH. An interaction model of human ribonuclease with the ribonuclease inhibitor, together with inhibition assays, indicate that, in contrast to RNase A, the modification of the loop beta4beta5 is not enough to avoid inhibition. This study represents the first crystallographic approach to the human enzyme, and should constitute an invaluable tool for the design of ribonuclease variants with acquired cytotoxic properties.
About this Structure
1DZA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases., Pous J, Canals A, Terzyan SS, Guasch A, Benito A, Ribo M, Vilanova M, Coll M, J Mol Biol. 2000 Oct 13;303(1):49-60. PMID:11021969
Page seeded by OCA on Sun Mar 30 19:51:47 2008
