1hkk: Difference between revisions

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 structure-based design of, specific allosamidin derivatives.

1HKK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and AMI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HKK OCA].  

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