DB code: S00202

RLCP classification	3.900.275800.990 : Transfer
CATH domain	3.20.20.80 : TIM Barrel	Catalytic domain
E.C.	2.4.1.25
CSA	1cwy
M-CSA	1cwy
MACiE

CATH domain	Related DB codes (homologues)
3.20.20.80 : TIM Barrel	S00210 S00748 S00906 S00907 S00911 S00912 S00915 M00134 M00160 D00479 S00204 S00205 S00206 S00207 S00203 S00208 S00209 S00211 S00213 S00214 M00113 T00307 D00165 D00166 D00169 D00176 D00501 D00502 D00503 D00844 D00861 D00864 M00026 M00112 M00193 M00346 T00057 T00062 T00063 T00066 T00067

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	CAZy	Pfam
O87172	4-alpha-glucanotransferase	EC 2.4.1.25 Amylomaltase Disproportionating enzyme D-enzyme	GH77 (Glycoside Hydrolase Family 77)	PF02446 (Glyco_hydro_77) [Graphical View]

KEGG enzyme name
4-alpha-glucanotransferase disproportionating enzyme dextrin glycosyltransferase D-enzyme debranching enzyme maltodextrin glycosyltransferase amylomaltase dextrin transglycosylase 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
O87172	MALQ_THETH	Transfers a segment of a (1->4)-alpha-D-glucan to a new position in an acceptor, which may be glucose or a (1->4)-alpha-D-glucan.		Cytoplasm (By similarity).

KEGG Pathways
Map code	Pathways	E.C.
MAP00500	Starch and sucrose metabolism

Compound table
	Substrates		Products	Intermediates
KEGG-id	C00718	C00293	C00208
E.C.
Compound	Amylose	Glucose	Maltose
Type	polysaccharide	carbohydrate	polysaccharide
ChEBI			17306 17306
PubChem			439186 439186

1cwyA	Unbound	Unbound	Unbound
1eswA	Analogue:ACR_651	Unbound	Unbound
1fp8A	Unbound	Unbound	Unbound
1fp9A	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
literature [11]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1cwyA	ASP 293;GLU 340;HIS 394;ASP 395
1eswA	ASP 293;GLU 340;HIS 394;ASP 395
1fp8A	ASP 293;GLU 340;HIS 394;ASP 395
1fp9A	ASP 293;GLU 340;HIS 394;ASP 395

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[7]	p.1057
[10]	p.6910-6911
[11]	Fig.1, p.879-882

References
[1]
Resource
Comments
Medline ID
PubMed ID	2086786
Journal	J Protozool
Year	1990
Volume	37
Pages	576-80
Authors	Werries E, Franz A, Geisemeyer S
Title	Detection of glycogen-debranching system in trophozoites of Entamoeba histolytica
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	7678257
Journal	J Biol Chem
Year	1993
Volume	268
Pages	1391-6
Authors	Takaha T, Yanase M, Okada S, Smith SM
Title	Disproportionating enzyme (4-alpha-glucanotransferase; EC 2.4.1.25) of potato. Purification, molecular cloning, and potential role in starch metabolism
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	85430201
Journal	FEBS Lett
Year	1995
Volume	377
Pages	6-8
Authors	Janecek S
Title	Close evolutionary relatedness among functionally distantly related members of the (alpha/beta)8-barrel glycosyl hydrolases suggested by the similarity of their fifth conserved sequence region
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	8621678
Journal	J Biol Chem
Year	1996
Volume	271
Pages	2902-8
Authors	Takaha T, Yanase M, Takata H, Okada S, Smith SM
Title	Potato D-enzyme catalyzes the cyclization of amylose to produce cycloamylose, a novel cyclic glucan
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	9353929
Journal	Microbiology
Year	1997
Volume	143
Pages	3287-94
Authors	Goda SK, Eissa O, Akhtar M, Minton NP
Title	Molecular analysis of a Clostridium butyricum NCIMB 7423 gene encoding 4-alpha-glucanotransferase and characterization of the recombinant enzyme produced in Escherichia coli
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	9642157
Journal	Biochem Biophys Res Commun
Year	1998
Volume	247
Pages	493-7
Authors	Takaha T, Yanase M, Takata H, Okada S, Smith SM
Title	Cyclic glucans produced by the intramolecular transglycosylation activity of potato D-enzyme on amylopectin
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	9990324
Journal	Eur J Biochem
Year	1998
Volume	258
Pages	1050-8
Authors	Meissner H, Liebl W
Title	Thermotoga maritima maltosyltransferase, a novel type of maltodextrin glycosyltransferase acting on starch and malto-oligosaccharides
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	10049841
Journal	Appl Environ Microbiol
Year	1999
Volume	65
Pages	910-5
Authors	Terada Y, Fujii K, Takaha T, Okada S
Title	Thermus aquaticus ATCC 33923 amylomaltase gene cloning and expression and enzyme characterization
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	10380338
Journal	Biopolymers
Year	1999
Volume	50
Pages	145-51
Authors	Nakatani H
Title	Monte Carlo simulation of 4-alpha-glucanotransferase reaction
Related PDB
Related UniProtKB
[10]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	11082203
Journal	Eur J Biochem
Year	2000
Volume	267
Pages	6903-13
Authors	Przylas I, Terada Y, Fujii K, Takaha T, Saenger W, Strater N
Title	X-ray structure of acarbose bound to amylomaltase from Thermus aquaticus. Implications for the synthesis of large cyclic glucans
Related PDB	1esw
Related UniProtKB
[11]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID	20143895
PubMed ID	10677288
Journal	J Mol Biol
Year	2000
Volume	296
Pages	873-86
Authors	Przylas I, Tomoo K, Terada Y, Takaha T, Fujii K, Saenger W, Strater N
Title	Crystal structure of amylomaltase from thermus aquaticus, a glycosyltransferase catalysing the production of large cyclic glucans
Related PDB	1cwy
Related UniProtKB	O87172

Comments
This enzyme is homologous to glycosidase family-13, to which alpha-amylase belongs. This family has a retaining mechanism. These structures would be a part of Glycogen Debranching Enzyme System that has both of 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities. This enzyme can catalyze the cyclization of amylose, with intramolecular transfer reaction. The reaction proceeds as follows (see [11]): (1) Glu340 acts as a general acid to protonate the glycosidic oxygen atom of the scissile bond, forming a oxocarbenium-like transition state. Here, Asp395 and His394 probably stabilize the transition state. (SN1-like reaction) (2) Asp293 acts as a nucleophile to make an attack on the C1 atom of the substrate, forming the covalent intermediate. (3) Glu340 now acts as a general base, to deprotonate the acceptor group, hydroxyl group. (4) The activated acceptor group makes another nucleophilic attack on the C1 atom, to form a new covalent bond.

Comments

This enzyme is homologous to glycosidase family-13, to which alpha-amylase belongs. This family has a retaining mechanism.
These structures would be a part of Glycogen Debranching Enzyme System that has both of 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities.
This enzyme can catalyze the cyclization of amylose, with intramolecular transfer reaction. The reaction proceeds as follows (see [11]):
(1) Glu340 acts as a general acid to protonate the glycosidic oxygen atom of the scissile bond, forming a oxocarbenium-like transition state. Here, Asp395 and His394 probably stabilize the transition state. (SN1-like reaction)
(2) Asp293 acts as a nucleophile to make an attack on the C1 atom of the substrate, forming the covalent intermediate.
(3) Glu340 now acts as a general base, to deprotonate the acceptor group, hydroxyl group.
(4) The activated acceptor group makes another nucleophilic attack on the C1 atom, to form a new covalent bond.

Created	Updated
2004-03-22	2011-11-30