1czi
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CHYMOSIN COMPLEX WITH THE INHIBITOR CP-113972
OverviewOverview
In the crystal structure of uncomplexed native chymosin, the beta-hairpin, at the active site, known as 'the flap', adopts a different conformation, from that of other aspartic proteinases. This conformation would prevent, the mode of binding of substrates/inhibitors generally found in other, aspartic proteinase complexes. We now report the X-ray analysis of, chymosin complexed with a reduced bond inhibitor CP-113972 inverted, question mark(2R,3S)-isopropyl, 3-[(L-prolyl-p-iodo-L-phenylalanyl-S-methyl-cysteinyl)amino-4]-cyclohexy, l-2-hydroxybutanoate inverted question mark at 2.3 A resolution in a novel, crystal form of spacegroup R32. The structure has been refined by, restrained least-squares methods to a final R-factor of 0.19 for a total, of 11 988 independent reflections in the resolution range 10 to 2.3 A. The, extended beta-strand conformation of the inhibitor allows hydrogen bonds, within the active site, while its sidechains make both electrostatic and, hydrophobic interactions with residues lining the specificity pockets, S4-->S1. The flap closes over the active site cleft in a way that closely, resembles that of other previously determined aspartic proteinase, inhibitor complexes. We conclude that the usual position and conformation, of the flap found in other aspartic proteinases is available to native, chymosin. The conformation observed in the native crystal form may result, from intermolecular interactions between symmetry-related molecules in the, crystal lattice.
About this StructureAbout this Structure
1CZI is a Single protein structure of sequence from Bos taurus. Active as Chymosin, with EC number 3.4.23.4 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
ReferenceReference
A 2.3 A resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure., Groves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL, Protein Eng. 1998 Oct;11(10):833-40. PMID:9862200
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