PDBsum entry: 1wb0

Hydrolase

PDB-id: 1wb0

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

365 a.a. *

Ligands

RAG

IPA

SO4 ×4

GOL

Waters ×224

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1wb0

Name:

Hydrolase

Title:

Specificity and affinity of natural product cyclopentapeptide inhibitor argifin against human chitinase

Structure:

Chitotriosidase 1. Chain: a. Synonym: chitinase 1. Ec: 3.2.1.14

Source:

Homo sapiens. Human. Organism_taxid: 9606

UniProt:

Q13231 (CHIT1_HUMAN)

Seq:

Struc:

Seq:

466 a.a.

Struc:

365 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Enzyme class:

E.C.3.2.1.14   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

Hydrolysis of the 1,4-beta-linkages of N-acetyl-D-glucosamine polymers of chitin.

Resolution:

1.65Å

R-factor:

0.178

R-free:

0.188

Authors:

F.V.Rao,D.R.Houston,R.G.Boot,J.M.F.G.Aerts,M.Hodkinson, D.J.Adams,K.Shiomi,S.Omura,D.M.F.Van Aalten

Key ref:

F.V.Rao et al. (2005). Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases.. Chem Biol, 12, 65-76. [PubMed id: 15664516] [DOI: 10.1016/j.chembiol.2004.10.013]

Date:

29-Oct-04

Release date:

28-Jan-05

Related entries:

1guv structure of human chitotriosidase
1hki crystal structure of human chitinase in complex with glucoallosamidin b
1hkj crystal structure of human chitinase in complex with methylallosamidin
1hkk high resoultion crystal structure of human chitinase in complex with allosamidin
1hkm high resoultion crystal structure of human chitinase in complex with demethylallosamidin
1lg1 crystal structure of human chitotriosidase in complex withchitobiose
1lg2 crystal structure of human chitotriosidase in complex withethylene glycol
1lq0 crystal structure of human chitotriosidase at 2.2 angstromresolution
1waw specificity and affnity of natural product cyclopentapeptide inhibitor argadin against human chitinase

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1016/j.chembiol.2004.10.013

Chem Biol 12:65-76 (2005)

PubMed id: 15664516

Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases.

F.V.Rao, D.R.Houston, R.G.Boot, J.M.Aerts, M.Hodkinson, D.J.Adams, K.Shiomi, S.Omura, D.M.van Aalten.

ABSTRACT

Family 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds.

Selected figure(s)

Figure 1.
Figure 1. Chemical Structures of Argifin and Argadin

Figure 2.
Figure 2. Structure of AfChiB1

The above figures are reprinted by permission from Cell Press: Chem Biol (2005, 12, 65-76) copyright 2005.

Figures were selected by an automated process.