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
| ISSN: | 1741-0134 1741-0126 0269-2139 |
|---|---|
| DOI: | 10.1093/protein/11.10.833 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6fee8fd6d169af041c07b6f849fe8896 https://doi.org/10.1093/protein/11.10.833 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....6fee8fd6d169af041c07b6f849fe8896 |
| Autor: | Dennis J. Hoover, Mohammed O. Badasso, Philip Nugent, Tom L. Blundell, V. Dhanaraj, J. E. Pitts, Matthew Groves |
| Přispěvatelé: | Drug Design, Medicinal Chemistry and Bioanalysis (MCB) |
| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Protein Conformation Stereochemistry Beta hairpin Static Electricity Bioengineering Crystal structure Crystallography X-Ray Biochemistry Hydrophobic effect Protein structure Renin Animals Humans Cysteine Chymosin Binding site Molecular Biology Binding Sites biology Hydrogen bond Chemistry Active site Hydrogen Bonding Butyrates Crystallography biology.protein Cattle Crystallization Protein Binding Biotechnology |
| Zdroj: | University of Groningen Protein Engineering, 11(10), 833-840 |
| ISSN: | 1741-0134 1741-0126 0269-2139 |
| DOI: | 10.1093/protein/11.10.833 |
| Popis: | 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 ¿(2R,3S)-isopropyl 3-[(L-prolyl-p-iodo-L-phenylalanyl-S-methyl-cysteinyl)amino-4]-cyclohexy l-2-hydroxybutanoate¿ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|