1dlk
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(New page: 200px<br /><applet load="1dlk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dlk, resolution 2.14Å" /> '''CRYSTAL STRUCTURE AN...)
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Revision as of 11:16, 20 November 2007
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CRYSTAL STRUCTURE ANALYSIS OF DELTA-CHYMOTRYPSIN BOUND TO A PEPTIDYL CHLOROMETHYL KETONE INHIBITOR
Overview
Chymotrypsin is a member of the trypsin family of serine proteases and is, one of the first proteins successfully studied by X-ray crystallography., It is secreted into the intestine as the inactive precursor, chymotrypsinogen; four sequential cleavages of the peptide bonds following, residues 13, 15, 146 and 148 occur to generate the active pi, delta, kappa, and alpha forms of chymotrypsin. (13)C NMR has shown [O'Connell &, Malthouse (1995). Biochem. J. 307, 353-359] that when the delta form of, chymotrypsin is inhibited by 2-(13)C-enriched, benzyloxycarbonylglycylglycylphenylalanyl chloromethane, a tetrahedral, adduct is formed which is thought to be analogous to the tetrahedral, intermediate formed during catalysis. This inhibitor complex has been, crystallized as a dimer in space group P4(1)2(1)2. The structure has been, refined at 2.14 A resolution to an R value of 21.2% (free R = 25.2%)., Conformational differences between delta-chymotrypsin and chymotrypsinogen, in the region of the flexible autolysis loop (residues 145-150) were, observed. This is the first crystal structure of delta-chymotrypsin and, includes two residues which are disordered in previous crystal structures, of active chymotrypsin. A difference of 11.3 A(2) between the average B, values of the monomers within the asymmetric unit is caused by, lattice-disordering effects approximating to rotation of the molecules, about a crystallographic screw axis. The substrate-binding mode of the, inhibitor was similar to other chymotrypsin peptidyl inhibitor complexes, but this is the first published chymotrypsin structure in which the, tetrahedral chloromethyl ketone transition-state analogue is observed., This structure is compared with that of a similar tetrahedral, transition-state analogue which does not alkylate the active-site, histidine residue.
About this Structure
1DLK is a Single protein structure of sequence from Bos taurus with CL, GLY and BGG as ligands. Active as Chymotrypsin, with EC number 3.4.21.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of delta-chymotrypsin bound to a peptidyl chloromethyl ketone inhibitor., Mac Sweeney A, Birrane G, Walsh MA, O'Connell T, Malthouse JP, Higgins TM, Acta Crystallogr D Biol Crystallogr. 2000 Mar;56(Pt 3):280-6. PMID:10713514
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