Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate - PubMed (original) (raw)
Comparative Study
. 1989 Sep 19;28(19):7610-7.
doi: 10.1021/bi00445a016.
Affiliations
- PMID: 2611205
- DOI: 10.1021/bi00445a016
Comparative Study
Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate
L H Takahashi et al. Biochemistry. 1989.
Abstract
The crystal structure of porcine pancreatic elastase (PPE) complexed to carbobenzoxy-alanylisoleucine-boronic acid (ZAIB) is reported to 2.09-A resolution and refined to an R factor of 0.15. This is the first reported structural analysis of PPE with an isoleucine residu in the primary specificity pocket. The results include (1) marked displacement of the inhibitor out of the active site leading to (2) a close (2.2 A) direct contact between B (boron atom of the inhibitor) and N epsilon of His-57 and also (3) covalent bonding (1.5 A) to O gamma of Ser-195. A scheme for the mechanism of inhibition of PPE by ZAIB is proposed. A comparison with a peptidyl difluoromethyl ketone-PPE complex (Ki = 9.5 microns) is made to explain the strong inhibition of PPE by ZAIB (Ki = 0.3 micron). These results lead us to characterize this structure as a time- and space-averaged reaction intermediate, providing fresh insight into the cramped dimensions available in enzymatic catalyses.
Similar articles
- Structural study of porcine pancreatic elastase complexed with 7-amino-3-(2-bromoethoxy)-4-chloroisocoumarin as a nonreactivatable doubly covalent enzyme-inhibitor complex.
Vijayalakshmi J, Meyer EF Jr, Kam CM, Powers JC. Vijayalakshmi J, et al. Biochemistry. 1991 Feb 26;30(8):2175-83. doi: 10.1021/bi00222a022. Biochemistry. 1991. PMID: 1998677 - X-ray diffraction analysis of the inhibition of porcine pancreatic elastase by a peptidyl trifluoromethylketone.
Takahashi LH, Radhakrishnan R, Rosenfield RE Jr, Meyer EF Jr, Trainor DA, Stein M. Takahashi LH, et al. J Mol Biol. 1988 May 20;201(2):423-8. doi: 10.1016/0022-2836(88)90148-9. J Mol Biol. 1988. PMID: 3418704 - Crystal structure of an elastase-specific inhibitor elafin complexed with porcine pancreatic elastase determined at 1.9 A resolution.
Tsunemi M, Matsuura Y, Sakakibara S, Katsube Y. Tsunemi M, et al. Biochemistry. 1996 Sep 10;35(36):11570-6. doi: 10.1021/bi960900l. Biochemistry. 1996. PMID: 8794736 - Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors.
Bode W, Meyer E Jr, Powers JC. Bode W, et al. Biochemistry. 1989 Mar 7;28(5):1951-63. doi: 10.1021/bi00431a001. Biochemistry. 1989. PMID: 2655701 Review. No abstract available. - Locating and characterizing binding sites on proteins.
Mattos C, Ringe D. Mattos C, et al. Nat Biotechnol. 1996 May;14(5):595-9. doi: 10.1038/nbt0596-595. Nat Biotechnol. 1996. PMID: 9630949 Review.
Cited by
- Probing contacts of inhibitor locked in transition states in the catalytic triad of DENV2 type serine protease and its mutants by 1H, 19F and 15 N NMR spectroscopy.
Agback P, Woestenenk E, Agback T. Agback P, et al. BMC Mol Cell Biol. 2020 May 25;21(1):38. doi: 10.1186/s12860-020-00283-0. BMC Mol Cell Biol. 2020. PMID: 32450796 Free PMC article. - Caspase-14 reveals its secrets.
Denecker G, Ovaere P, Vandenabeele P, Declercq W. Denecker G, et al. J Cell Biol. 2008 Feb 11;180(3):451-8. doi: 10.1083/jcb.200709098. Epub 2008 Feb 4. J Cell Biol. 2008. PMID: 18250198 Free PMC article. Review. - Direct crystallographic observation of an acyl-enzyme intermediate in the elastase-catalyzed hydrolysis of a peptidyl ester substrate: Exploiting the "glass transition" in protein dynamics.
Ding X, Rasmussen BF, Petsko GA, Ringe D. Ding X, et al. Bioorg Chem. 2006 Dec;34(6):410-23. doi: 10.1016/j.bioorg.2006.10.002. Epub 2006 Nov 2. Bioorg Chem. 2006. PMID: 17083959 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources