1z5f

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Revision as of 02:37, 25 November 2007

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Solution Structure of the Cytotoxic RC-RNase 3 with a Pyroglutamate Residue at the N-terminus

Overview

Many proteins and bioactive peptides contain an N-terminal pyroglutamate, residue (Pyr1). This residue reduces the susceptibility of the protein to, aminopeptidases and often has important functional roles. The antitumor, ribonuclease RC-RNase 3 (RNase 3) from oocytes of Rana catesbeiana, (bullfrog) is one such protein. We have produced recombinant RNase 3, containing the N-terminal Pyr1 (pRNase 3) and found it to be, indistinguishable from the native RNase 3 by mass spectrometry and a, variety of other biochemical and immunological criteria. We demonstrated, by NMR analysis that the Pyr1 of pRNase 3 forms hydrogen bonds with Lys9, and Ile96 and stabilizes the N-terminal alpha-helix in a rigid, conformation. In contrast, the N-terminal alpha-helix becomes flexible and, the pKa values of the catalytic residues His10 and His97 altered when Pyr1, formation is blocked by an extra methionine at the N terminus in the, recombinant mqRNase 3. Thus, our results provide a mechanistic explanation, on the essential role of Pyr1 in maintaining the structural integrity, especially at the N-terminal alpha-helix, and in providing the proper, environment for the ionization of His10 and His97 residues for catalysis, and cytotoxicity against HeLa cells.

About this Structure

1Z5F is a Single protein structure of sequence from Rana catesbeiana. Full crystallographic information is available from OCA.

Reference

Roles of N-terminal pyroglutamate in maintaining structural integrity and pKa values of catalytic histidine residues in bullfrog ribonuclease 3., Lou YC, Huang YC, Pan YR, Chen C, Liao YD, J Mol Biol. 2006 Jan 20;355(3):409-21. Epub 2005 Nov 10. PMID:16309702

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