Two polymorphs of a covalent complex between papain and a diazomethylketone inhibitor.
The three-dimensional structure of two polymorphs of a ZLFG-CH2-papain covalent complex has been determined by X-ray crystallography. The structures indicate that: (i) the methylene carbon atom of the inhibitor is covalently bound to the Sgamma atom of Cys25 of papain; (ii) the hydrophobic S2 pocket formed by Pro68, Val133, Val157, and Asp158 is occupied by the inhibitor's phenylalanyl P2 side chain; (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. Comparison with similar structures suggests that in covalent complexes preservation of main chain-main chain interactions between the enzyme and the inhibitor may have higher priority than the P-S interactions.
Janowski
R
R
Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań, Poland.
Kozak
M
M
Jankowska
E
E
Grzonka
Z
Z
Jaskólski
M
M
D001665:Binding Sites; D002855:Chromatography, Thin Layer; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry; D019992:Databases as Topic; D003978:Diazomethane / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004583:Electrons; D006860:Hydrogen Bonding; D007659:Ketones / Q000737:chemistry; D008958:Models, Molecular; D010206:Papain / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry; D013379:Substrate Specificity
D007659:Ketones; D003978:Diazomethane; D003546:Cysteine Endopeptidases; D010206:Papain