1H0I

Complex of a chitinase with the natural product cyclopentapeptide argifin from Gliocladium

Summary for 1H0I

• Entry DOI: 10.2210/pdb1h0i/pdb
• Related: 1H0G
• Related PRD ID: PRD_000465
• Descriptor: CHITINASE B, ARGIFIN, GLYCEROL, ... (5 entities in total)
• Functional Keywords: hydrolase-inhibitor complex, hydrolase, chitin degradation, argifin, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: SERRATIA MARCESCENS; More
• Total number of polymer chains: 4
• Total formula weight: 114088.78

Authors

Houston, D.R.,Shiomi, K.,Arai, N.,Omura, S.,Peter, M.G.,Turberg, A.,Synstad, B.,Eijsink, V.G.H.,Aalten, D.M.F. (deposition date: 2002-06-19, release date: 2002-06-27, Last modification date: 2024-02-07)

Primary citation

Houston, D.R.,Shiomi, K.,Arai, N.,Omura, S.,Peter, M.G.,Turberg, A.,Synstad, B.,Eijsink, V.G.H.,Van Aalten, D.M.F.
High Resolution Inhibited Complexes of a Chitinase with Natural Product Cyclopentapeptides - Peptide Mimicry of a Carbohydrate Substrate
Proc.Natl.Acad.Sci.USA, 99:9127-, 2002

PubMed Abstract: Over the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry.

PubMed: 12093900
DOI: 10.1073/PNAS.132060599

Experimental method

X-RAY DIFFRACTION (2 Å)