The structure of allosamidin, a novel insect chitinase inhibitor, produced by Streptomyces Sp.

Sakuda, Shohei; Isogai, Akira; Matsumoto, Shogo; Suzuki, Akira; Koseki, Koshi

doi:10.1016/s0040-4039(00)84560-8

Cited by 214 publications

(133 citation statements)

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“…It has a unique pseudotrisaccharide structure mimic to chitin [2] and inhibits all family 18 chitinases, which hydrolyze chitin and are widely present in nature [3]. Allosamidin has been used to investigate the physiological role of chitinases involved not only in chitin-containing organisms, but also in nonchitin-containing ones.…”

Section: Introductionmentioning

confidence: 99%

Chitinase Inhibitor Allosamidin Is a Signal Molecule for Chitinase Production in Its Producing Streptomyces

et al. 2006

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Allosamidin, a typical secondary metabolite of Streptomyces, has been known as a chitinase inhibitor. We found that allosamidin can dramatically promote chitinase production and growth of its producer, Streptomyces sp. AJ9463, in a chitin medium at a few hundred nM. Allosamidin promoted production of the main chitinase detected in the culture filtrate and the chitin-hydrolytic activity of the chitinase was not inhibited by allosamidin at the concentration. The gene encoding the chitinase showed that it is a family 18 chitinase and it was revealed that two genes encoding proteins constructing two-component regulatory system were present at 5Ј-upstream region of the chitinase gene. Allosamidin is located in the microbial mycelia cultured in a medium without chitin, but it was released from the mycelia by responding to chitin. These results show that allosamidin acts as a key signal molecule for chitinase production in its producing strain, which may be useful for its growth in chitin-rich environment.

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Section: Introductionmentioning

confidence: 99%

Chitinase Inhibitor Allosamidin Is a Signal Molecule for Chitinase Production in Its Producing Streptomyces

et al. 2006

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“…Chitin is not found in humans but plays a key role in the life cycles of several classes of human pathogens, such as fungi (1), nematodes (2), protozoan parasites (3), and insects (4). Several chitinase inhibitors with biological activity have been identified, such as allosamidin (5), styloguanidines (6), and the cyclic peptides CI-4 (7-9), argifin (10), and argadin (11,12). Allosamidin (see Fig.…”

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Crystal Structures of Allosamidin Derivatives in Complex with Human Macrophage Chitinase

Rao

Houston

Boot

et al. 2003

Journal of Biological Chemistry

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The pseudotrisaccharide allosamidin is a potent family 18 chitinase inhibitor with demonstrated biological activity against insects, fungi, and the Plasmodium falciparum life cycle. The synthesis and biological properties of several derivatives have been reported. The structural interactions of allosamidin with several family 18 chitinases have been determined by x-ray crystallography previously. Here, a high resolution structure of chitotriosidase, the human macrophage chitinase, in complex with allosamidin is presented. In addition, complexes of the allosamidin derivatives demethylallosamidin, methylallosamidin, and glucoallosamidin B are described, together with their inhibitory properties. Similar to other chitinases, inhibition of the human chitinase by allosamidin derivatives lacking a methyl group is 10-fold stronger, and smaller effects are observed for the methyl and C3 epimer derivatives. The structures explain the effects on inhibition in terms of altered hydrogen bonding and hydrophobic interactions, together with displaced water molecules. The data reported here represent a first step toward structurebased design of specific allosamidin derivatives.

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“…Just as inhibitors of chitin synthesis have been shown to possess antifungal properties, a class of chitinase inhibitors has been described and found to have affects on whole cells. Allosamidin, derived from the fermentation of a Streptomyces isolate not identified to species level, was first reported as an inhibitor of insect chitinase (140,205,206). The purified material was reported to inhibit the enzyme from the silkworm Bombyx mon in a competitive fashion in the micromolar range and was lethal to caterpillars at a dose of 10 ,ug per larva.…”

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 99%

Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

215

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A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

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The structure of allosamidin, a novel insect chitinase inhibitor, produced by Streptomyces Sp.

Cited by 214 publications

References 0 publications

Chitinase Inhibitor Allosamidin Is a Signal Molecule for Chitinase Production in Its Producing Streptomyces

Chitinase Inhibitor Allosamidin Is a Signal Molecule for Chitinase Production in Its Producing Streptomyces

Crystal Structures of Allosamidin Derivatives in Complex with Human Macrophage Chitinase

Compounds active against cell walls of medically important fungi

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