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2bd2
From Proteopedia
| 2bd2, resolution 1.70Å () | |||||||||
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| Ligands: | , , , | ||||||||
| Activity: | Pancreatic elastase, with EC number 3.4.21.36 | ||||||||
| Related: | 1hax, 1hay, 1haz, 1qix, 2bb4, 2bd3, 2bd4, 2bd5, 2bd6, 2bd7, 2bd8, 2bd9, 2bda, 2bdb, 2bdc | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Porcine pancreatic elastase complexed with beta-casomorphin-7 and Arg-Phe at pH 5.0
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.
Structural analyses on intermediates in serine protease catalysis., Liu B, Schofield CJ, Wilmouth RC, J Biol Chem. 2006 Aug 18;281(33):24024-35. Epub 2006 Jun 5. PMID:16754679
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2bd2 is a 2 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA.
See Also
Reference
- Liu B, Schofield CJ, Wilmouth RC. Structural analyses on intermediates in serine protease catalysis. J Biol Chem. 2006 Aug 18;281(33):24024-35. Epub 2006 Jun 5. PMID:16754679 doi:10.1074/jbc.M600495200
- Wilmouth RC, Clifton IJ, Robinson CV, Roach PL, Aplin RT, Westwood NJ, Hajdu J, Schofield CJ. Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase. Nat Struct Biol. 1997 Jun;4(6):456-62. PMID:9187653
- Wilmouth RC, Edman K, Neutze R, Wright PA, Clifton IJ, Schneider TR, Schofield CJ, Hajdu J. X-ray snapshots of serine protease catalysis reveal a tetrahedral intermediate. Nat Struct Biol. 2001 Aug;8(8):689-94. PMID:11473259 doi:10.1038/90401
