1h0g

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{{STRUCTURE_1h0g| PDB=1h0g | SCENE= }}
{{STRUCTURE_1h0g| PDB=1h0g | SCENE= }}
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'''COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGADIN FROM CLONOSTACHYS'''
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===COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGADIN FROM CLONOSTACHYS===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12093900 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12093900}}
==About this Structure==
==About this Structure==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
[[Category: Inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:15:20 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:24:51 2008''

Revision as of 03:24, 1 July 2008

Image:1h0g.png

Template:STRUCTURE 1h0g

COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGADIN FROM CLONOSTACHYS

Template:ABSTRACT PUBMED 12093900

About this Structure

1H0G is a Protein complex structure of sequences from Serratia marcescens. Full crystallographic information is available from OCA.

Reference

High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate., Houston DR, Shiomi K, Arai N, Omura S, Peter MG, Turberg A, Synstad B, Eijsink VG, van Aalten DM, Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9127-32. Epub 2002 Jul 1. PMID:12093900

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