1guv: Difference between revisions

Revision as of 13:54, 21 February 2008

STRUCTURE OF HUMAN CHITOTRIOSIDASE

OverviewOverview

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.

About this StructureAbout this Structure

1GUV is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

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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OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Aalten, D.M.F.Van.]]
+[[Category: Aalten, D M.F Van.]]
-[[Category: Aerts, J.M.F.G.]]
+[[Category: Aerts, J M.F G.]]
-[[Category: Boot, R.G.]]
+[[Category: Boot, R G.]]
 [[Category: Houston, D.]]
-[[Category: Moeller, H.Von.]]
+[[Category: Moeller, H Von.]]
 [[Category: EDO]]
 [[Category: chitin degradation]]
@@ Line 24: / Line 24: @@
 [[Category: lectin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:42:53 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:11 2008''