1guv

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{{STRUCTURE_1guv| PDB=1guv | SCENE= }}
{{STRUCTURE_1guv| PDB=1guv | SCENE= }}
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'''STRUCTURE OF HUMAN CHITOTRIOSIDASE'''
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===STRUCTURE OF HUMAN CHITOTRIOSIDASE===
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==Overview==
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Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors.
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(as it appears on PubMed at http://www.pubmed.gov), where 11960986 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11960986}}
==About this Structure==
==About this Structure==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Lectin]]
[[Category: Lectin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:02:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:07:22 2008''

Revision as of 03:07, 1 July 2008

Image:1guv.png

Template:STRUCTURE 1guv

STRUCTURE OF HUMAN CHITOTRIOSIDASE

Template:ABSTRACT PUBMED 11960986

About this Structure

1GUV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins., Fusetti F, von Moeller H, Houston D, Rozeboom HJ, Dijkstra BW, Boot RG, Aerts JM, van Aalten DM, J Biol Chem. 2002 Jul 12;277(28):25537-44. Epub 2002 Apr 17. PMID:11960986

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