1O6I

Chitinase B from Serratia marcescens complexed with the catalytic intermediate mimic cyclic dipeptide CI4.

Summary for 1O6I

• Entry DOI: 10.2210/pdb1o6i/pdb
• Related: 1H0G 1H0I
• Descriptor: Chitinase, amino({3-[(3S,8aS)-1,4-dioxooctahydropyrrolo[1,2-a]pyrazin-3-yl]propyl}amino)methaniminium, GLYCEROL, ... (5 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, chitinase, catalytic intermediate mimic, cyclic dipeptide, hydrolase- hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Serratia marcescens
• Total number of polymer chains: 2
• Total formula weight: 114975.93

Authors

Houston, D.R.,Eggleston, I.,Synstad, B.,Eijsink, V.G.H.,van Aalten, D.M.F. (deposition date: 2002-10-03, release date: 2003-03-30, Last modification date: 2024-11-13)

Primary citation

Houston, D.R.,Eggleston, I.,Synstad, B.,Eijsink, V.G.,van Aalten, D.M.
The cyclic dipeptide CI-4 [cyclo-(l-Arg-d-Pro)] inhibits family 18 chitinases by structural mimicry of a reaction intermediate.
Biochem. J., 368:23-27, 2002

PubMed Abstract: Family 18 chitinases are attractive targets for the development of new inhibitors with chemotherapeutic potential against fungi, insects and protozoan/nematodal parasites. Although several inhibitors have been identified, these are based on complex chemistry, which hampers iterative structure-based optimization. Here we report the details of chitinase inhibition by the natural product peptide CI-4 [ cyclo -(L-Arg-D-Pro)], which possesses activity against the human pathogenic fungus Candida albicans, and describe a 1.7 A (0.17 nm) crystal structure of CI-4 in complex with the enzyme. The structure reveals that the cyclic dipeptide inhibits chitinases by structurally mimicking a reaction intermediate, and could, on the basis of its accessible chemistry, be a candidate for further optimization.

PubMed: 12323074
DOI: 10.1042/BJ20021034

Experimental method

X-RAY DIFFRACTION (1.7 Å)