2BDB
Porcine pancreatic elastase complexed with Asn-Pro-Ile and Ala-Ala at pH 5.0
Summary for 2BDB
| Entry DOI | 10.2210/pdb2bdb/pdb |
| Related | 1GVK 1QIX 2BB4 2BD2 2BD3 2BD4 2BD5 2BD6 2BD7 2BD8 2BD9 2BDA 2BDC |
| Descriptor | Elastase-1, CALCIUM ION, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | serine proteinase, hydrolase |
| Biological source | Sus scrofa (pig) |
| Cellular location | Secreted: P00772 |
| Total number of polymer chains | 1 |
| Total formula weight | 26242.36 |
| Authors | Liu, B.,Schofield, C.J.,Wilmouth, R.C. (deposition date: 2005-10-20, release date: 2006-05-30, Last modification date: 2023-10-25) |
| Primary citation | Liu, B.,Schofield, C.J.,Wilmouth, R.C. Structural analyses on intermediates in serine protease catalysis J.Biol.Chem., 281:24024-24035, 2006 Cited by PubMed Abstract: Although the subject of many studies, detailed structural information on aspects of the catalytic cycle of serine proteases is lacking. Crystallographic analyses were performed in which an acyl-enzyme complex, formed from elastase and a peptide, was reacted with a series of nucleophilic dipeptides. Multiple analyses led to electron density maps consistent with the formation of a tetrahedral species. In certain cases, apparent peptide bond formation at the active site was observed, and the electron density maps suggested production of a cis-amide rather than a trans-amide. Evidence for a cis-amide configuration was also observed in the noncovalent complex between elastase and an alpha1-antitrypsin-derived tetrapeptide. Although there are caveats on the relevance of the crystallographic data to solution catalysis, the results enable detailed proposals for the pathway of the acylation step to be made. At least in some cases, it is proposed that the alcohol of Ser-195 may preferentially attack the carbonyl of the cis-amide form of the substrate, in a stereoelectronically favored manner, to give a tetrahedral oxyanion intermediate, which undergoes N-inversion and/or C-N bond rotation to enable protonation of the leaving group nitrogen. The mechanistic proposals may have consequences for protease inhibition, in particular for the design of high energy intermediate analogues. PubMed: 16754679DOI: 10.1074/jbc.M600495200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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