1HAX

Snapshots of serine protease catalysis: (A) acyl-enzyme intermediate between porcine pancreatic elastase and human beta-casomorphin-7 at pH 5

Summary for 1HAX

• Entry DOI: 10.2210/pdb1hax/pdb
• Related: 1B0E 1BMA 1BTU 1C1M 1E34 1E35 1E36 1E37 1E38 1EAI 1EAS 1EAT 1EAU 1ELA 1ELB 1ELC 1ELD 1ELE 1ELF 1ELG 1ESA 1ESB 1EST 1FLE 1H9L 1HAY 1HAZ 1HB0 1HV7 1INC 1JIM 1LVY 1NES 1QGF 1QIX 1QNJ 1QR3 2EST 3EST 4EST 5EST 6EST 7EST 8EST 9EST
• Descriptor: BETA-CASOMORPHIN-7, ELASTASE 1, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, serine proteinase, hydrolase (serine proteinase)
• Biological source: SUS SCROFA (PIG); More
• Cellular location: Secreted: P00772
• Total number of polymer chains: 2
• Total formula weight: 26606.82

Authors

Wilmouth, R.C.,Edman, K.,Neutze, R.,Wright, P.A.,Clifton, I.J.,Schneider, T.R.,Schofield, C.J.,Hajdu, J. (deposition date: 2001-04-10, release date: 2001-08-02, Last modification date: 2023-12-13)

Primary citation

Wilmouth, R.C.,Edman, K.,Neutze, R.,Wright, P.A.,Clifton, I.J.,Schneider, T.R.,Schofield, C.J.,Hajdu, J.
X-Ray Snapshots of Serine Protease Catalysis Reveal a Tetrahedral Intermediate
Nat.Struct.Biol., 8:689-, 2001

PubMed Abstract: Studies on the catalytic mechanism and inhibition of serine proteases are widely used as paradigms for teaching enzyme catalysis. Ground-breaking work on the structures of chymotrypsin and subtilisin led to the idea of a conserved catalytic triad formed by the active site Ser, His and Asp residues. An oxyanion hole, consisting of the peptide amide of the active site serine and a neighbouring glycine, was identified, and hydrogen bonding in the oxyanion hole was suggested to stabilize the two proposed tetrahedral intermediates on the catalytic pathway. Here we show electron density changes consistent with the formation of a tetrahedral intermediate during the hydrolysis of an acyl-enzyme complex formed between a natural heptapeptide and elastase. No electron density for an enzyme-product complex was observed. The structures also suggest a mechanism for the synchronization of hydrolysis and peptide release triggered by the conversion of the sp2 hybridized carbonyl carbon to an sp3 carbon in the tetrahedral intermediate. This affects the location of the peptide in the active site cleft, triggering the collapse of a hydrogen bonding network between the peptide and the beta-sheet of the active site.

PubMed: 11473259
DOI: 10.1038/90401

Experimental method

X-RAY DIFFRACTION (1.6 Å)