PDBsum entry: 1w1v

Hydrolase

PDB-id: 1w1v

Biological unit = asymmetric unit, as shown
(as defined in PDB file)

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PROCHECK

Protein chains

497 a.a. *

Ligands

GOL ×31

SO4 ×2

ALJ ×2

Waters ×707

* Residue conservation analysis

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Clefts Calculation

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PDB id:

1w1v

Name:

Hydrolase

Title:

Crystal structure of s. Marcescens chitinase b in complex with the cyclic dipeptide inhibitor cyclo-(l-arg-l-pro) at 1.85 a resolution

Structure:

Chitinase b. Chain: a, b. Engineered: yes

Source:

Serratia marcescens. Organism_taxid: 615. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Biological unit:

Dimer (from PDB file)

UniProt:

Chains A, B: Q54276 (Q54276_SERMA)

Seq:

Struc:

Seq:

499 a.a.

Struc:

497 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

1.85Å

R-factor:

0.187

R-free:

0.213

Authors:

D.R.Houston,B.Synstad,V.G.H.Eijsink,I.Eggleston, D.M.F.Van Aalten

Key ref:

D.R.Houston et al. (2004). Structure-based exploration of cyclic dipeptide chitinase inhibitors.. J Med Chem, 47, 5713-5720. [PubMed id: 15509170] [DOI: 10.1021/jm049940a]

Date:

24-Jun-04

Release date:

10-Jan-05

Related entries:

1e15 chitinase b from serratia marcescens
1e6n chitinase b from serratia marcescens inactive mutant e144q in complex with n- acetylglucosamine-pentamer
1e6p chitinase b from serratia marcescens inactive mutant e144q
1e6r chitinase b from serratia marcescens wildtype in complex with inhibitor allosamidin
1e6z chitinase b from serratia marcescens wildtype in complex with catalytic intermediate
1goi crystal structure of the d140n mutant of chitinase b from serratia marcescens at 1. 45 a resolution
1gpf chitinase b from serratia marcescens in complex with inhibitor psammaplin
1ogb structure of the d142n mutant of the family 18 chitinase chib from serratia marcescens and its complex with allosamidin
1ur8 interactions of a family 18 chitinase with the designed inhibitor hm508, and its degradation product, chitobiono-delta-lactone
1ur9 interactions of a family 18 chitinase with the designed inhibitor hm508, and its degradation product, chitobiono-delta-lactone
... plus others (see Header records)

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Key reference

DOI no: 10.1021/jm049940a

J Med Chem 47:5713-5720 (2004)

PubMed id: 15509170

Structure-based exploration of cyclic dipeptide chitinase inhibitors.

D.R.Houston, B.Synstad, V.G.Eijsink, M.J.Stark, I.M.Eggleston, D.M.van Aalten.

ABSTRACT

Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 inhibits family 18 chitinases by mimicking the structure of the proposed reaction intermediate. Here we report the high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro) substructure is sufficient for binding, allowing modification of the side chain of the nonproline residue. This suggests that design of cyclic dipeptides with a view to increasing inhibition of family 18 chitinases should be possible through relatively accessible chemistry. The derivatives presented here in complex with chitinase B from Serratia marcescens provide further insight into the mechanism of inhibition of chitinases by cyclic dipeptides as well as providing a new scaffold for chitinase inhibitor design.