1PE6

REFINED X-RAY STRUCTURE OF PAPAIN(DOT)E-64-C COMPLEX AT 2.1-ANGSTROMS RESOLUTION

Summary for 1PE6

• Entry DOI: 10.2210/pdb1pe6/pdb
• Descriptor: PAPAIN, N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-2-METHYL-BUTANE, METHANOL, ... (4 entities in total)
• Functional Keywords: hydrolase (sulfhydryl proteinase)
• Biological source: Carica papaya (papaya)
• Total number of polymer chains: 1
• Total formula weight: 24214.33

Authors

Yamamoto, D.,Matsumoto, K.,Ohishi, H.,Ishida, T.,Inoue, M.,Kitamura, K.,Mizuno, H. (deposition date: 1991-05-14, release date: 1993-04-15, Last modification date: 2024-11-06)

Primary citation

Yamamoto, D.,Matsumoto, K.,Ohishi, H.,Ishida, T.,Inoue, M.,Kitamura, K.,Mizuno, H.
Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution.
J.Biol.Chem., 266:14771-14777, 1991

PubMed Abstract: E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.

PubMed: 1860874

Experimental method

X-RAY DIFFRACTION (2.1 Å)