2AIM

CRUZAIN INHIBITED WITH BENZOYL-ARGININE-ALANINE-FLUOROMETHYLKETONE

Summary for 2AIM

• Entry DOI: 10.2210/pdb2aim/pdb
• Descriptor: CRUZAIN, BENZOYL-ARGININE-ALANINE-FLUORO-METHYL KETONE (3 entities in total)
• Functional Keywords: cysteine protease, trypanosoma cruzi, proteinase, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 1
• Total formula weight: 23112.58

Authors

Gillmor, S.A.,Fletterick, R.J. (deposition date: 1997-04-21, release date: 1997-10-22, Last modification date: 2024-10-30)

Primary citation

Gillmor, S.A.,Craik, C.S.,Fletterick, R.J.
Structural determinants of specificity in the cysteine protease cruzain.
Protein Sci., 6:1603-1611, 1997

PubMed Abstract: The structure of cruzain, an essential protease from the parasite Trypanosoma cruzi, was determined by X-ray crystallography bound to two different covalent inhibitors. The cruzain S2 specificity pocket is able to productively bind both arginine and phenylalanine residues. The structures of cruzain bound to benzoyl-Arg-Ala-fluoromethyl ketone and benzoyl-Tyr-Ala-fluoromethyl ketone at 2.2 and 2.1 A, respectively, show a pH-dependent specificity switch. Glu 205 adjusts to restructure the S2 specificity pocket, conferring right binding to both hydrophobic and basic residues. Kinetic analysis of activated peptide substrates shows that substrates placing hydrophobic residues in the specificity pocket are cleaved at a broader pH range than hydrophilic substrates. These results demonstrate how cruzain binds both basic and hydrophobic residues and could be important for in vivo regulation of cruzain activity.

PubMed: 9260273

Experimental method

X-RAY DIFFRACTION (2.2 Å)