3AHN

PZ PEPTIDASE A with Inhibitor 1

Summary for 3AHN

• Entry DOI: 10.2210/pdb3ahn/pdb
• Related: 3AHM 3AHO
• Related PRD ID: PRD_000668
• Descriptor: Oligopeptidase, N~2~-{(2S)-3-[(R)-hydroxy{(1R)-2-phenyl-1-[(phenylacetyl)amino]ethyl}phosphoryl]-2-methylpropanoyl}-L-lysyl-D-serine, ZINC ION, ... (5 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Geobacillus sp. MO-1
• Total number of polymer chains: 2
• Total formula weight: 134608.52

Authors

Nakano, H. (deposition date: 2010-04-25, release date: 2010-08-25, Last modification date: 2024-02-21)

Primary citation

Kawasaki, A.,Nakano, H.,Hosokawa, A.,Nakatsu, T.,Kato, H.,Watanabe, K.
The exquisite structure and reaction mechanism of bacterial Pz-peptidase A toward collagenous peptides: X-ray crystallographic structure analysis of PZ-peptidase a reveals differences from mammalian thimet oligopeptidase.
J.Biol.Chem., 285:34972-34980, 2010

PubMed Abstract: Pz-peptidase A, from the thermophilic bacterium Geobacillus collagenovorans MO-1, hydrolyzes a synthetic peptide substrate, 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-PLGPR), which contains a collagen-specific tripeptide sequence, -Gly-Pro-X-, but does not act on collagen proteins themselves. The mammalian enzyme, thimet oligopeptidase (TOP), which has comparable functions with bacterial Pz-peptidases but limited identity at the primary sequence level, has recently been subjected to x-ray crystallographic analysis; however, no crystal structure has yet been reported for complexes of TOP with substrate analogues. Here, we report crystallization of recombinant Pz-peptidase A in complex with two phosphinic peptide inhibitors (PPIs) that also function as inhibitors of TOP and determination of the crystal structure of these complexes at 1.80-2.00 Å resolution. The most striking difference between Pz-peptidase A and TOP is that there is no channel running the length of bacterial protein. Whereas the structure of TOP resembles an open bivalve, that of Pz-peptidase A is closed and globular. This suggests that collagenous peptide substrates enter the tunnel at the top gateway of the closed Pz-peptidase A molecule, and reactant peptides are released from the bottom gateway after cleavage at the active site located in the center of the tunnel. One of the two PPIs, PPI-2, which contains the collagen-specific sequence, helped to clarify the exquisite structure and reaction mechanism of Pz-peptidase A toward collagenous peptides. This study describes the mode of substrate binding and its implication for the mammalian enzymes.

PubMed: 20817732
DOI: 10.1074/jbc.M110.141838

Experimental method

X-RAY DIFFRACTION (1.8 Å)