Analysis of productive binding modes in the human chitotriosidase

Eide, Kristine Bistrup; Lindbom, Anne Rita; Eijsink, Vincent G. H.; Norberg, Anne Line; Sørlie, Morten

doi:10.1016/j.febslet.2013.09.004

Cited by 23 publications

(23 citation statements)

References 35 publications

(94 reference statements)

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“…Ec Chi1 synthesized long-chain CHOS even with low concentrations of substrate and enzyme. Amino acid residues positioned at acceptor binding site are assumed to be crucial for TG activity 43 . The known chitinases with TG activity were occupied with aromatic amino acids at +n subsites.…”

Section: Discussionmentioning

confidence: 99%

Transglycosylation by a chitinase from Enterobacter cloacae subsp. cloacae generates longer chitin oligosaccharides

Mallakuntla

Vaikuntapu

Bhuvanachandra

et al. 2017

Sci Rep

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Humans have exploited natural resources for a variety of applications. Chitin and its derivative chitin oligosaccharides (CHOS) have potential biomedical and agricultural applications. Availability of CHOS with the desired length has been a major limitation in the optimum use of such natural resources. Here, we report a single domain hyper-transglycosylating chitinase, which generates longer CHOS, from Enterobacter cloacae subsp. cloacae 13047 (EcChi1). EcChi1 was optimally active at pH 5.0 and 40 °C with a Km of 15.2 mg ml−1, and k cat/Km of 0.011× 102 mg−1 ml min−1 on colloidal chitin. The profile of the hydrolytic products, major product being chitobiose, released from CHOS indicated that EcChi1 was an endo-acting enzyme. Transglycosylation (TG) by EcChi1 on trimeric to hexameric CHOS resulted in the formation of longer CHOS for a prolonged duration. EcChi1 showed both chitobiase and TG activities, in addition to hydrolytic activity. The TG by EcChi1 was dependent, to some extent, on the length of the CHOS substrate and concentration of the enzyme. Homology modeling and docking with CHOS suggested that EcChi1 has a deep substrate-binding groove lined with aromatic amino acids, which is a characteristic feature of a processive enzyme.

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Section: Discussionmentioning

confidence: 99%

Transglycosylation by a chitinase from Enterobacter cloacae subsp. cloacae generates longer chitin oligosaccharides

Mallakuntla

Vaikuntapu

Bhuvanachandra

et al. 2017

Sci Rep

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“…6 ). Tryptophan is known to be involved in stacking interactions with sugar in the active site of carbohydrate active enzymes (Eide et al 2013 ; Larsson et al 2006 ). Most likely, there is a combination of factors in the structure of AnMan5B that contribute to high transglycosylation capacity, where R206, analogous to R171 in TrMan5A, might play one of the roles in providing affinity in the aglycone subsites, potentially together with W242.…”

Section: Discussionmentioning

confidence: 99%

An Aspergillus nidulans β-mannanase with high transglycosylation capacity revealed through comparative studies within glycosidase family 5

Rosengren

Reddy

Sjöberg

et al. 2014

Appl Microbiol Biotechnol

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β-Mannanases are involved in the conversion and modification of mannan-based saccharides. Using a retaining mechanism, they can, in addition to hydrolysis, also potentially perform transglycosylation reactions, synthesizing new glyco-conjugates. Transglycosylation has been reported for β-mannanases in GH5 and GH113. However, although they share the same fold and catalytic mechanism, there may be differences in the enzymes’ ability to perform transglycosylation. Three GH5 β-mannanases from Aspergillus nidulans, AnMan5A, AnMan5B and AnMan5C, which belong to subfamily GH5_7 were studied. Comparative studies, including the GH5_7 TrMan5A from Trichoderma reesei, showed some differences between the enzymes. All the enzymes could perform transglycosylation but AnMan5B stood out in generating comparably higher amounts of transglycosylation products when incubated with manno-oligosaccharides. In addition, AnMan5B did not use alcohols as acceptor, which was also different compared to the other three β-mannanases. In order to map the preferred binding of manno-oligosaccharides, incubations were performed in H218O. AnMan5B in contrary to the other enzymes did not generate any 18O-labelled products. This further supported the idea that AnMan5B potentially prefers to use saccharides as acceptor instead of water. A homology model of AnMan5B showed a non-conserved Trp located in subsite +2, not present in the other studied enzymes. Strong aglycone binding seems to be important for transglycosylation with saccharides. Depending on the application, it is important to select the right enzyme.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-014-5871-8) contains supplementary material, which is available to authorized users.

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“…The enzyme was initially thought to be an exochitinase because it can hydrolyze chitotriose residues and was termed chitotriosidase based on this observation. However, recent structural and binding modes studies revealed the enzyme to be more of an endochitinase rather than an exochitinase [ 29 , 30 ]. Furthermore, the strong binding affinity of chitotriosidase to its substrate is also responsible for the relatively high transglycosylation activity of the enzyme even in the absence of excess substrate concentrations, making chitotriosidase a complete independent chitinolytic machinery, and this is in accordance with its anticipated physiological role as a potent immunological defense weapon against microorganisms containing chitin [ 31 , 32 ].…”

Section: Chemistry and Modes Of Actionmentioning

confidence: 99%

Immunomodulatory Effects of Chitotriosidase Enzyme

2016

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Chitotriosidase enzyme (EC: 3.2.1.14) is the major active chitinase in the human body. It is produced mainly by activated macrophages, in which its expression is regulated by multiple intrinsic and extrinsic signals. Chitotriosidase was confirmed as essential element in the innate immunity against chitin containing organisms such as fungi and protozoa; however, its immunomodulatory effects extend far beyond innate immunity. In the current review, we will try to explore the expanding spectrum of immunological roles played by chitotriosidase enzyme in human health and disease and will discuss its up-to-date clinical value.

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Analysis of productive binding modes in the human chitotriosidase

Cited by 23 publications

References 35 publications

Transglycosylation by a chitinase from Enterobacter cloacae subsp. cloacae generates longer chitin oligosaccharides

Transglycosylation by a chitinase from Enterobacter cloacae subsp. cloacae generates longer chitin oligosaccharides

An Aspergillus nidulans β-mannanase with high transglycosylation capacity revealed through comparative studies within glycosidase family 5

Immunomodulatory Effects of Chitotriosidase Enzyme

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