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Information on EC 3.2.1.14 - chitinase and Organism(s) Homo sapiens and UniProt Accession Q9BZP6

for references in articles please use BRENDA:EC3.2.1.14
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EC Tree
     3 Hydrolases
         3.2 Glycosylases
             3.2.1 Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds
                3.2.1.14 chitinase
IUBMB Comments
The enzyme binds to chitin and randomly cleaves glycosidic linkages in chitin and chitodextrins in a non-processive mode, generating chitooligosaccharides and free ends on which exo-chitinases and exo-chitodextrinases can act. Activity is greatly stimulated in the presence of EC 1.14.99.53, lytic chitin monoxygenase, which attacks the crystalline structure of chitin and makes the polymer more accesible to the chitinase. cf. EC 3.2.1.202, endo-chitodextrinase.
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Homo sapiens
UNIPROT: Q9BZP6
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
chitinase, chitotriosidase, endochitinase, antifreeze protein, chit1, amcase, chitinase a, exochitinase, acidic mammalian chitinase, class i chitinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acidic mammalian chitinase
-
1,4-beta-poly-N-acetylglucosaminidase
-
-
-
-
acid mammalian chitinase
-
-
acidic mammalian chitinase
-
-
beta-1,4-poly-N-acetyl glucosamidinase
-
-
-
-
CF-AG
-
-
-
-
CF-antigen
-
-
-
-
CHI-26
-
-
-
-
CHIT 1A
-
-
-
-
CHIT 1B
-
-
-
-
chitodextrinase-N-
-
-
-
-
chitotriosidase
-
-
Complement-fixation antigen
-
-
-
-
endochitinase
-
-
-
-
MF1 antigen
-
-
-
-
poly-beta-glucosaminidase
-
-
-
-
SI-CLP
-
-
stabilin-1 interacting chitinase-like protein
-
-
UDA
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Random endo-hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins
show the reaction diagram
catalytic reaction mechanism involving Glu119, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of O-glycosyl bond
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
(1->4)-2-acetamido-2-deoxy-beta-D-glucan glycanohydrolase
The enzyme binds to chitin and randomly cleaves glycosidic linkages in chitin and chitodextrins in a non-processive mode, generating chitooligosaccharides and free ends on which exo-chitinases and exo-chitodextrinases can act. Activity is greatly stimulated in the presence of EC 1.14.99.53, lytic chitin monoxygenase, which attacks the crystalline structure of chitin and makes the polymer more accesible to the chitinase. cf. EC 3.2.1.202, endo-chitodextrinase.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-06-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(GlcNAc)6 + H2O
(GlcNAc)2 + (GlcNAc)3 + (GlcNAc)4
show the reaction diagram
the enzyme prefers the beta-anomer of chito-oligosaccharides as substrate, cleavage of beta-glycosidic linkages from the non-reducing end primarily by disaccharide units
product analysis
-
r
4-methylumbelliferyl 2-acetamido-4-O-(2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranosyl)-2-deoxy-beta-D-glucopyranoside + H2O
4-methylumbelliferol + 2-acetamido-4-O-(2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranosyl)-2-deoxy-beta-D-glucopyranoside
show the reaction diagram
-
-
-
?
4-methylumbelliferyl beta-N,N',N''-triacetylchitotrioside + H2O
4-methylumbelliferol + beta-N,N',N''-triacetylchitotriose
show the reaction diagram
-
product analysis
-
?
4-methylumbelliferyl beta-N,N'-diacetylchitobioside + H2O
4-methylumbelliferol + beta-N,N'-diacetylchitobiose
show the reaction diagram
-
product analysis
-
?
chitin + H2O
?
show the reaction diagram
-
-
-
r
2-acetamido-2-deoxy-4-O-(2-acetamido-2-deoxy-4-O-methyl-beta-D-glucopyranosyl)-1-O-4-methylumbelliferyl-beta-D-glucopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
2-acetamido-2-deoxy-4-O-(2-acetamido-4-O-cyclohexylmethyl-2-deoxy-beta-D-glucopyranosyl)-1-O-4-methylumbelliferyl-beta-D-glucopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
2-acetamido-2-deoxy-4-O-(2-deoxy-2-acetamido-4-O-isopropyl-beta-D-glucopyranosyl)-1-O-4-methylumbelliferyl-beta-D-glucopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl beta-N,N'-diacetylchitobioside + H2O
4-methylumbelliferol + N,N'-diacetylchitobiose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl chitobioside + H2O
4-methylumbelliferone + chitobiose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-beta-D-N,N'-diacetylchitobiose + H2O
4-methylumbelliferone + N,N'-diacetylchitobiose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside + H2O
4-methylumbelliferone + N,N'-diacetylchitobiose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-D-N,N'-diacetylchito-bioside + H2O
4-methylumbelliferone + D-N,N'-diacetylchito-bioside
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-N,N'N''-triacetyl-beta-chitotrioside + H2O
? + 4-methylumbelliferone
show the reaction diagram
-
-
-
-
?
carboxymethyl-substituted chitin labeled with Remazol Brilliant Violet + H2O
?
show the reaction diagram
-
-
-
-
?
chitin + H2O
?
show the reaction diagram
chitin azure + H2O
?
show the reaction diagram
-
-
-
-
?
fluorescein isothiocyanate chitin + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl beta-D-N',N'',N'''-triacetylchitotriose + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl-beta-D-N,N'-diacetylchitobiose + H2O
N,N'-diacetylchitobiose + p-nitrophenol
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
chitin + H2O
?
show the reaction diagram
-
-
-
r
chitin + H2O
?
show the reaction diagram
-
substrate of CHITI1 and AMCase, the polysaccharide is contained in many human parasites
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
allosamidin
modelling of ligand binding at the active site, Glu119 forms hydrogen bond with allosamidin. Trp10, Glu49, Asp192, and Glu276 in hAMCase are four important determinant residues in binding as they form strong van der Waals and electrostatic interactions with the ligand, respectively
methylallosamidin
complex formation with the enzyme and binding structure analysis, overview
2-(piperazin-1-yl)pyridine-3-carboxamide
-
-
2-methyl-3-[[4-(pyridin-2-yl)piperazin-1-yl]methyl]-1H-indole
-
-
4-(4-chlorophenyl)piperazine-1-carboximidamide
-
-
5-[4-[2-(4-bromophenoxy)ethyl]piperazin-1-yl]-1H-1,2,4-triazol-3-amine
-
-
allosamidin
-
inhibits by direct blocking of the enzyme or blocking of target binding
methylallosamidin
-
-
N-ethyl-2-(4-methylpiperazin-1-yl)pyridine-3-carboxamide
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
dexamethasone, cytokine Th2 and interleukin IL-4 strongly up-regulate SI-CLP in macrophages, the effect is suppressed by IFNgamma but not by IL-10
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 0.171
4-methylumbelliferyl 2-acetamido-4-O-(2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranosyl)-2-deoxy-beta-D-glucopyranoside
0.032
4-methylumbelliferyl chitobioside
-
pH 5.0, 25°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05 - 1.83
4-methylumbelliferyl 2-acetamido-4-O-(2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranosyl)-2-deoxy-beta-D-glucopyranoside
3
4-methylumbelliferyl chitobioside
-
pH 5.0, 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.09
4-methylumbelliferyl chitobioside
-
pH 5.0, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000057
methylallosamidin
Homo sapiens
-
pH 5.0, 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
104.6
-
39 kDa form
additional information
-
AMCase activity is present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h. In the remaining five of 25 gastric juices, AMCase activity is almost absent
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 5
recombinant AMCAse
4 - 5.2
-
assay at, substrate-dependent
5.2
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2 - 8
recombinant AMCase is inactive below pH 2.0 and above pH 8.0
2
-
30% of maximum activity
3.5
-
30% of maximum activity
6.5
-
30% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
25
-
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
significantly higher serum chitotriosidase activity in sarcoidosis patients than in controls and in sarcoidosis patients than tuberculosis patients. The enzyme may be specifically involved in the pathogenesis of sarcoidosis
Manually annotated by BRENDA team
-
in bronchoalveolar lavage
Manually annotated by BRENDA team
-
recombinant enzyme
Manually annotated by BRENDA team
-
AMCase activity is present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h. In the remaining five of 25 gastric juices, AMCase activity is almost absent
Manually annotated by BRENDA team
-
peripheral
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
from a type I Gaucher patient
Manually annotated by BRENDA team
-
high expression of isoform CHIA, no expression of pseudogene CHIA-L1
Manually annotated by BRENDA team
additional information
-
expression in human cell lines, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
secretory
Manually annotated by BRENDA team
additional information
-
SI-CLP expression analysis, colocalization of SI-CLP with stabilin-1 in the trans Golgi network
-
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CHIA_HUMAN
476
0
52271
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
39000
-
x * 39000, SDS-PAGE, x * 50000, SDS-PAGE
50000
-
x * 39000, SDS-PAGE, x * 50000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
N-glycosylation at Ser354
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
AMCase catalytic domain in the apo form and in complex with the inhibitor methylallosamidin, X-ray diffraction structure determination and analysis at 1.7-2.0 A resolution
three-dimensional modeling of variant isoforms. The overall protein fold is not altered in mutant N45D/D47N/R61M
purified recombinant enzyme in complex with inhibitor 1, hanging drop vapor diffusion, 0.0002 ml of protein solution containing 0.44 mM AMCase, 0.52 mM inhibitor 1, 25 mM Tris-HCl, pH 8.0, and 50 mM NaCl, is mixed with 0.0002 ml of reservoir solution containing 20% PEG MME 5000, 100 mM bis-Tris, equilibration over 0.2 ml of reservoir solution, pH 6.5, 18°C, 2 weeks, X-ray diffraction structure determination and analysis, modeling
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N45D/D47N/R61M
natural mutant based on single nucleotide polymorphisms. The mutant is 4-, 2.5-, and 10fold more active than the wild type AMCase isoform at pH 2.2, 4.6, and 7.0, respectively
S354F
site-directed mutagenesis of the glycosylation site rsidue
A442G
-
isolation and analysis of the naturally occurring polymorphism of isozyme CHIT1 from Caucasian children with bronchial asthma and adult control individuals, the mutation does not play a major role in development of asthma in children
G102S
-
isolation and analysis of the naturally occurring polymorphism of isozyme CHIT1 from Caucasian children with bronchial asthma and adult control individuals, the mutation does not play a major role in development of asthma in children
additional information
-
mutation of the chitin-cleaving domain abolishes the chitinase activity, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged AMCase from CHO cells by nickel affinity and hydrophobic interaction chromatography, and gel filtration
3630fold, 39 kDa form
-
recombinant enzyme from BHK cell culture supernatant by ultrafiltration and concanavalin A affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene CHIA, expression of His-tagged AMCase in CHO cells
CHIT1, DNA and amino acid sequence determination and analysis
-
enzyme expression in BHK cells and secretion to the culture medium
-
expression in A-549 cells
-
stable expression of SI-CLP in H1299 cells, SI-CLP expression analysis in human cell lines, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
resequencing of all 12 AMCase exons in three diverse populations: African Americans, Puerto Ricans, and Mexicans leads to identification of 21 variants including four 5-untranslated region variants, nine non-synonymous single nucleotide polymorphisms, four synonymous single nucleotide polymorphisms, a 3-untranslated region single nucleotide polymorphism, and three intronic single nucleotide polymorphisms. Among the non-synonymous single nucleotide polymorphisms eight variants are common to all three racial groups single nucleotide polymorphisms: A290G, N45D, G296A, D47N, G339T, R61M, G461A, G102R, A531G, K125R, G1172A, V339I, T1218C, F354S, and G1452T, G432V. Minimal linkage disequilibrium is exhibited between these variants with the exception of single nucleotide polymorphisms A290G, G296A, and G339T. The G339T single nucelotide polymorphism is associated with asthma protection in some populations
pharmacology
hAMCase is a potential therapeutic target for anti-inflammatory therapy in Th2-mediated diseases such as asthma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Renkema, G.H.; Boot, R.G.; Muijsers, A.O.; Donker-Koopman, W.E.; Aerts, J.M.F.G.
Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins
J. Biol. Chem.
270
2198-2202
1995
Homo sapiens
Manually annotated by BRENDA team
Chou, Y.T.; Yao, S.; Czerwinski, R.; Fleming, M.; Krykbaev, R.; Xuan, D.; Zhou, H.; Brooks, J.; Fitz, L.; Strand, J.; Presman, E.; Lin, L.; Aulabaugh, A.; Huang, X.
Kinetic characterization of recombinant human acidic mammalian chitinase
Biochemistry
45
4444-4454
2006
Homo sapiens (Q9BZP6), Homo sapiens
Manually annotated by BRENDA team
Kzhyshkowska, J.; Mamidi, S.; Gratchev, A.; Kremmer, E.; Schmuttermaier, C.; Krusell, L.; Haus, G.; Utikai, J.; Schledzewski, K.; Scholtze, J.; Goerdt, S.
Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway
Blood
107
3221-3228
2006
Homo sapiens
Manually annotated by BRENDA team
Bierbaum, S.; Superti-Furga, A.; Heinzmann, A.
Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthma
Int. J. Immunogenet.
33
201-204
2006
Homo sapiens
Manually annotated by BRENDA team
Paoletti, M.G.; Norberto, L.; Damini, R.; Musumeci, S.
Human gastric juice contains chitinase that can degrade chitin
Ann. Nutr. Metab.
51
244-251
2007
Homo sapiens
Manually annotated by BRENDA team
Bargagli, E.; Margollicci, M.; Nikiforakis, N.; Luddi, A.; Perrone, A.; Grosso, S.; Rottoli, P.
Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis
Respiration
74
548-552
2007
Homo sapiens
Manually annotated by BRENDA team
Ghauharali-van der Vlugt, K.; Bussink, A.P.; Groener, J.E.; Boot, R.G.; Aerts, J.M.
Detection of chitinase activity by 2-aminobenzoic acid labeling of chito-oligosaccharides
Anal. Biochem.
384
191-193
2009
Homo sapiens
Manually annotated by BRENDA team
Hartl, D.; He, C.H.; Koller, B.; Da Silva, C.A.; Kobayashi, Y.; Lee, C.G.; Flavell, R.A.; Elias, J.A.
Acidic mammalian chitinase regulates epithelial cell apoptosis via a chitinolytic-independent mechanism
J. Immunol.
182
5098-5106
2009
Homo sapiens
Manually annotated by BRENDA team
Zhao, Y.S.; Zheng, Q.C.; Zhang, H.X.; Chu, H.Y.; Sun, C.C.
Analysis of a three-dimensional structure of human acidic mammalian chitinase obtained by homology modeling and ligand binding studies
J. Mol. Model.
15
499-505
2009
Homo sapiens (Q9BZP6), Homo sapiens
Manually annotated by BRENDA team
Olland, A.M.; Strand, J.; Presman, E.; Czerwinski, R.; Joseph-McCarthy, D.; Krykbaev, R.; Schlingmann, G.; Chopra, R.; Lin, L.; Fleming, M.; Kriz, R.; Stahl, M.; Somers, W.; Fitz, L.; Mosyak, L.
Triad of polar residues implicated in pH specificity of acidic mammalian chitinase
Protein Sci.
18
569-578
2009
Homo sapiens (Q9BZP6)
Manually annotated by BRENDA team
Krykbaev, R.; Fitz, L.J.; Reddy, P.S.; Winkler, A.; Xuan, D.; Yang, X.; Fleming, M.; Wolf, S.F.
Evolutionary and biochemical differences between human and monkey acidic mammalian chitinases
Gene
452
63-71
2010
Homo sapiens, Macaca fascicularis (D3GG13), Macaca fascicularis
Manually annotated by BRENDA team
Seibold, M.A.; Reese, T.A.; Choudhry, S.; Salam, M.T.; Beckman, K.; Eng, C.; Atakilit, A.; Meade, K.; Lenoir, M.; Watson, H.G.; Thyne, S.; Kumar, R.; Weiss, K.B.; Grammer, L.C.; Avila, P.; Schleimer, R.P.; Fahy, J.V.; Rodriguez-Santana, J.; Rodriguez-Cintron, W.; Boot, R.G.; Sheppard, D.; Gilliland, F.D.; et al.
Differential enzymatic activity of common haplotypic versions of the human acidic mammalian chitinase protein
J. Biol. Chem.
284
19650-19658
2009
Homo sapiens (Q9BZP6), Homo sapiens
Manually annotated by BRENDA team
Cole, D.C.; Olland, A.M.; Jacob, J.; Brooks, J.; Bursavich, M.G.; Czerwinski, R.; DeClercq, C.; Johnson, M.; Joseph-McCarthy, D.; Ellingboe, J.W.; Lin, L.; Nowak, P.; Presman, E.; Strand, J.; Tam, A.; Williams, C.M.; Yao, S.; Tsao, D.H.; Fitz, L.J.
Identification and characterization of acidic mammalian chitinase inhibitors
J. Med. Chem.
53
6122-6128
2010
Homo sapiens
Manually annotated by BRENDA team
Duivenvoorden, B.A.; Ghauharali, K.; Scheij, S.; Boot, R.G.; Aerts, J.M.; van der Marel, G.A.; Overkleeft, H.S.; Codee, J.D.
Design and synthesis of 4-O-alkyl-chitobiosyl-4-methylumbelliferone as human chitinase fluorogenic substrates
Carbohydr. Res.
399
26-37
2014
Homo sapiens
Manually annotated by BRENDA team