Glycoside Hydrolase Family 13 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:18:34Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Stefan Janecek at 14:44, 30 June 2014

2014-06-30T14:44:03Z

Stefan Janecek at 11:50, 7 February 2011

2011-02-07T11:50:27Z

Harry Brumer: /* Substrate specificities */ Added links out to CBM families.

2011-02-07T08:43:10Z

Substrate specificities: Added links out to CBM families.

Harry Brumer: /* Substrate specificities */

2011-02-07T08:38:08Z

Substrate specificities

Harry Brumer: /* Three-dimensional structures */

2011-02-07T08:37:06Z

Three-dimensional structures

Harry Brumer at 08:34, 7 February 2011

2011-02-07T08:34:25Z

Harry Brumer: /* Catalytic Residues */

2011-02-07T08:31:45Z

Catalytic Residues

Harry Brumer: /* Substrate specificities */

2011-02-07T08:30:11Z

Substrate specificities

Harry Brumer: /* Substrate specificities */

2011-02-07T08:28:03Z

Substrate specificities

@@ Line 1: / Line 1: @@
 {{CuratorApproved}}
-* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^
+* [[Author]]s: [[User:Birte Svensson|Birte Svensson]] and [[User:Stefan Janecek|Stefan Janecek]]
-* [[Responsible Curator]]:  ^^^Birte Svensson^^^
+* [[Responsible Curator]]:  [[User:Birte Svensson|Birte Svensson]]
 ----

@@ Line 90: / Line 90: @@
 #Jespersen1993 pmid=8136030
 #Takata1992 pmid=1388153
-#Nakajima1986 Nakajima R, Imanaka T, and Aiba S. ''Comparison of amino acid sequences of eleven different α-amylases.'' Appl Microbiol Biotechnol 1986; 23(5) 355-60. ([http://dx.doi.org/10.1007/BF00257032 DOI: 10.1007/BF00257032])
+#Nakajima1986 Nakajima R, Imanaka T, and Aiba S. ''Comparison of amino acid sequences of eleven different α-amylases.'' Appl Microbiol Biotechnol 1986; 23(5): 355-60. ([http://dx.doi.org/10.1007/BF00257032 DOI: 10.1007/BF00257032])
 #Janecek1992 pmid=1471979
 #Janecek1994a pmid=7925367
-#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11) 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])
+#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])
 #Kuriki1991 pmid=1917847
-#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])
+#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16): 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])
 #Janecek2007 pmid=17349635
 #Janecek1994b pmid=7926034
@@ Line 106: / Line 106: @@
 #Bowman1945 pmid=17730484
 #Svensson2004 pmid=14871655
-#Macri1993 Macri LJ, MacGregor AW, Schroeder SW, and Bazin SL. ''Detection of a limit dextrinase inhibitor in barley.'' J Cereal Sci 1993; 18(2) 103-6. ([http://dx.doi.org/10.1006/jcrs.1993.1038 DOI: 10.1006/jcrs.1993.1038])
+#Macri1993 Macri LJ, MacGregor AW, Schroeder SW, and Bazin SL. ''Detection of a limit dextrinase inhibitor in barley.'' J Cereal Sci 1993; 18(2): 103-6. ([http://dx.doi.org/10.1006/jcrs.1993.1038 DOI: 10.1006/jcrs.1993.1038])
 #MacGregor2003 MacGregor AW, Donald LJ, MacGregor EA, and Duckworth HW. ''Stoichiometry of the complex formed by barley limit dextrinase with its endogenous inhibitor. Determination by electrospray time-of-flight mass spectrometry.'' J Cereal Sci 2003; 37(3) 357-62. ([http://dx.doi.org/10.1006/jcrs.2002.0500 DOI: 10.1006/jcrs.2002.0500])
 #MacGregor2004 pmid=14871657
-#Kimura1983 Kimura A, and Chiba S. ''Quantitative study of anomeric forms of maltose produced by α- and β-amylases.'' Agric Biol Chem 1983; 47(8) 1747-53. ([http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=bbb1961&cdvol=47&noissue=8&startpage=1747 Link])
+#Kimura1983 Kimura A, and Chiba S. ''Quantitative study of anomeric forms of maltose produced by α- and β-amylases.'' Agric Biol Chem 1983; 47(8): 1747-53. ([http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=bbb1961&cdvol=47&noissue=8&startpage=1747 Link])
 #Isoda1992 pmid=1569044
 #Uitdehaag1999 pmid=10331869
@@ Line 119: / Line 119: @@
 #Prodanov1984 pmid=6611158
 #Ajandouz1992 pmid=1390923
-#MacGregor1992 Macgregor AW, Morgan JE, and Macgregor EA. ''The action of germinated barley α-amylases on linear maltodextrins.'' Carbohydr Res 1992; 227 301-13. ([http://dx.doi.org/10.1016/0008-6215(92)85080-J DOI: 10.1016/0008-6215(92)85080-J])
+#MacGregor1992 Macgregor AW, Morgan JE, and Macgregor EA. ''The action of germinated barley α-amylases on linear maltodextrins.'' Carbohydr Res 1992; 227: 301-13. ([http://dx.doi.org/10.1016/0008-6215(92)85080-J DOI: 10.1016/0008-6215(92)85080-J])
 #Kandra2006 pmid=16949579
 #Bozonnet2007 pmid=17803687

@@ Line 30: / Line 30: @@
 Family GH13 is the major [[glycoside hydrolase]]  family acting on substrates containing α-glucoside linkages. A number of reviews are concerned with α-amylases <cite>Svensson1994,Janecek1997a,Kuriki1999,MacGregor2001,vanderMaarel2002</cite>. GH13 contains hydrolases, transglycosidases and isomerases <cite>MacGregor2001</cite>; noticeably animal amino acid transporters <cite>Janecek1997b</cite>, which have no glycosidase activity <cite>Fort2007</cite>, are also GH13 members. The enzymes are found in a very wide range of organisms from all kingdoms. While known specificities are indicated by the enzyme named as listed below, for several of these numerous enzymes are characterized representing subspecificities defined by structural requirements for preferred substrates or the structure of the predominant product(s).
-Described enzymes include: α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]); oligo-1,6-glucosidase (EC [{{EClink}}3.2.1.10 3.2.1.10]); α-glucosidase (EC [{{EClink}}3.2.1.20 3.2.1.20]); pullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]); cyclomaltodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]); maltotetraose-forming α-amylase (EC [{{EClink}}3.2.1.60 3.2.1.60]); isoamylase (EC [{{EClink}}3.2.1.68 3.2.1.68]); dextran glucosidase (EC [{{EClink}}3.2.1.70 3.2.1.70]); trehalose-6-phosphate hydrolase (EC [{{EClink}}3.2.1.93 3.2.1.93]); maltohexaose-forming α-amylase (EC [{{EClink}}3.2.1.98 3.2.1.98]); maltotriose-forming α-amylase (EC [{{EClink}}3.2.1.116 3.2.1.116]); maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]); neopullulanase (EC [{{EClink}}3.2.1.135 3.2.1.135]); malto-oligosyltrehalose trehalohydrolase (EC [{{EClink}}3.2.1.141 3.2.1.141]); maltopentaose-forming α-amylase (EC [{{EClink}}3.2.1.- 3.2.1.-]); amylosucrase (EC [{{EClink}}2.4.1.4 2.4.1.4]); sucrose phosphorylase (EC [{{EClink}}2.4.1.7 2.4.1.7]); branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]); cyclomaltodextrin glucanotransferase (CGTase) (EC [{{EClink}}2.4.1.19 2.4.1.19]); 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]); isomaltulose synthase (EC [{{EClink}}5.4.99.11 5.4.99.11]); trehalose synthase (EC [{{EClink}}5.4.99.16 5.4.99.16]).
+Described enzymes include: α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]); oligo-1,6-glucosidase (EC [{{EClink}}3.2.1.10 3.2.1.10]); α-glucosidase (EC [{{EClink}}3.2.1.20 3.2.1.20]); pullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]); cyclomaltodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]); maltotetraose-forming α-amylase (EC [{{EClink}}3.2.1.60 3.2.1.60]); isoamylase (EC [{{EClink}}3.2.1.68 3.2.1.68]); dextran glucosidase (EC [{{EClink}}3.2.1.70 3.2.1.70]); trehalose-6-phosphate hydrolase (EC [{{EClink}}3.2.1.93 3.2.1.93]); maltohexaose-forming α-amylase (EC [{{EClink}}3.2.1.98 3.2.1.98]); maltotriose-forming α-amylase (EC [{{EClink}}3.2.1.116 3.2.1.116]); maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]); neopullulanase (EC [{{EClink}}3.2.1.135 3.2.1.135]); malto-oligosyltrehalose trehalohydrolase (EC [{{EClink}}3.2.1.141 3.2.1.141]); limit dextrinase (EC [{{EClink}}3.2.1.142 3.2.1.142]); maltopentaose-forming α-amylase (EC [{{EClink}}3.2.1.- 3.2.1.-]); amylosucrase (EC [{{EClink}}2.4.1.4 2.4.1.4]); sucrose phosphorylase (EC [{{EClink}}2.4.1.7 2.4.1.7]); branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]); cyclomaltodextrin glucanotransferase (CGTase) (EC [{{EClink}}2.4.1.19 2.4.1.19]); 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]); isomaltulose synthase (EC [{{EClink}}5.4.99.11 5.4.99.11]); trehalose synthase (EC [{{EClink}}5.4.99.16 5.4.99.16]).
 As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Notably, a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to [{{CAZyDBlink}}CBM20.html CBM20], [{{CAZyDBlink}}CBM21.html CBM21], [{{CAZyDBlink}}CBM25.html CBM25], [{{CAZyDBlink}}CBM26.html CBM26], [{{CAZyDBlink}}CBM34.html CBM34], [{{CAZyDBlink}}CBM41.html CBM41], [{{CAZyDBlink}}CBM45.html CBM45], [{{CAZyDBlink}}CBM48.html CBM48], [{{CAZyDBlink}}CBM53.html CBM53], and [{{CAZyDBlink}}CBM58.html CBM58] <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.

@@ Line 32: / Line 32: @@
 Described enzymes include: α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]); oligo-1,6-glucosidase (EC [{{EClink}}3.2.1.10 3.2.1.10]); α-glucosidase (EC [{{EClink}}3.2.1.20 3.2.1.20]); pullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]); cyclomaltodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]); maltotetraose-forming α-amylase (EC [{{EClink}}3.2.1.60 3.2.1.60]); isoamylase (EC [{{EClink}}3.2.1.68 3.2.1.68]); dextran glucosidase (EC [{{EClink}}3.2.1.70 3.2.1.70]); trehalose-6-phosphate hydrolase (EC [{{EClink}}3.2.1.93 3.2.1.93]); maltohexaose-forming α-amylase (EC [{{EClink}}3.2.1.98 3.2.1.98]); maltotriose-forming α-amylase (EC [{{EClink}}3.2.1.116 3.2.1.116]); maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]); neopullulanase (EC [{{EClink}}3.2.1.135 3.2.1.135]); malto-oligosyltrehalose trehalohydrolase (EC [{{EClink}}3.2.1.141 3.2.1.141]); maltopentaose-forming α-amylase (EC [{{EClink}}3.2.1.- 3.2.1.-]); amylosucrase (EC [{{EClink}}2.4.1.4 2.4.1.4]); sucrose phosphorylase (EC [{{EClink}}2.4.1.7 2.4.1.7]); branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]); cyclomaltodextrin glucanotransferase (CGTase) (EC [{{EClink}}2.4.1.19 2.4.1.19]); 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]); isomaltulose synthase (EC [{{EClink}}5.4.99.11 5.4.99.11]); trehalose synthase (EC [{{EClink}}5.4.99.16 5.4.99.16]).
-As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Notably, a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to CBM20, 21, 25, 26, 34, 41, 45, 48, 53, and 58 <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.
+As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Notably, a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to [{{CAZyDBlink}}CBM20.html CBM20], [{{CAZyDBlink}}CBM21.html CBM21], [{{CAZyDBlink}}CBM25.html CBM25], [{{CAZyDBlink}}CBM26.html CBM26], [{{CAZyDBlink}}CBM34.html CBM34], [{{CAZyDBlink}}CBM41.html CBM41], [{{CAZyDBlink}}CBM45.html CBM45], [{{CAZyDBlink}}CBM48.html CBM48], [{{CAZyDBlink}}CBM53.html CBM53], and [{{CAZyDBlink}}CBM58.html CBM58] <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.
 The GH13 enzymes have a wide range of different preferred substrates and products. For example, the α-amylases prefer polysaccharides of the α-1,4-glucan type, such as amylose and amylopectin, but are also able to attack the supramolecular structures represented by starch granules and glycogen particles. Besides they have some significant albeit slower turn-over of maltooligosaccharides of a certain degree of polymerization. These typical substrate profiles can be manipulated through protein engineering.

@@ Line 32: / Line 32: @@
 Described enzymes include: α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]); oligo-1,6-glucosidase (EC [{{EClink}}3.2.1.10 3.2.1.10]); α-glucosidase (EC [{{EClink}}3.2.1.20 3.2.1.20]); pullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]); cyclomaltodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]); maltotetraose-forming α-amylase (EC [{{EClink}}3.2.1.60 3.2.1.60]); isoamylase (EC [{{EClink}}3.2.1.68 3.2.1.68]); dextran glucosidase (EC [{{EClink}}3.2.1.70 3.2.1.70]); trehalose-6-phosphate hydrolase (EC [{{EClink}}3.2.1.93 3.2.1.93]); maltohexaose-forming α-amylase (EC [{{EClink}}3.2.1.98 3.2.1.98]); maltotriose-forming α-amylase (EC [{{EClink}}3.2.1.116 3.2.1.116]); maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]); neopullulanase (EC [{{EClink}}3.2.1.135 3.2.1.135]); malto-oligosyltrehalose trehalohydrolase (EC [{{EClink}}3.2.1.141 3.2.1.141]); maltopentaose-forming α-amylase (EC [{{EClink}}3.2.1.- 3.2.1.-]); amylosucrase (EC [{{EClink}}2.4.1.4 2.4.1.4]); sucrose phosphorylase (EC [{{EClink}}2.4.1.7 2.4.1.7]); branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]); cyclomaltodextrin glucanotransferase (CGTase) (EC [{{EClink}}2.4.1.19 2.4.1.19]); 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]); isomaltulose synthase (EC [{{EClink}}5.4.99.11 5.4.99.11]); trehalose synthase (EC [{{EClink}}5.4.99.16 5.4.99.16]).
-As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Noticeably a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to CBM20, 21, 25, 26, 34, 41, 45, 48, 53, and 58 <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.
+As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Notably, a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to CBM20, 21, 25, 26, 34, 41, 45, 48, 53, and 58 <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.
 The GH13 enzymes have a wide range of different preferred substrates and products. For example, the α-amylases prefer polysaccharides of the α-1,4-glucan type, such as amylose and amylopectin, but are also able to attack the supramolecular structures represented by starch granules and glycogen particles. Besides they have some significant albeit slower turn-over of maltooligosaccharides of a certain degree of polymerization. These typical substrate profiles can be manipulated through protein engineering.

← Older revision		Revision as of 08:37, 7 February 2011
Line 54:		Line 54:

	Among the solved structures are numerous site-directed-mutant and ligand-complexed forms. However, although there are structures available for most of the GH13 specificities, some still remain to be determined. Noticeably crystal structures are available of several α-amylase/proteinaceous inhibitor complexes (for reviews, see <cite>Svensson2004,Payan2004</cite>).		Among the solved structures are numerous site-directed-mutant and ligand-complexed forms. However, although there are structures available for most of the GH13 specificities, some still remain to be determined. Noticeably crystal structures are available of several α-amylase/proteinaceous inhibitor complexes (for reviews, see <cite>Svensson2004,Payan2004</cite>).
		+
		+	For a complete list of all currently available three-dimensional structures, please see the [{{CAZyDBlink}}GH13.html GH13 page in CAZy database], which is continuously updated.

	== Family Firsts ==		== Family Firsts ==

@@ Line 21: / Line 21: @@
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 |-
-| colspan="2" |http://www.cazy.org/fam/GH13.html
+| colspan="2" |{{CAZyDBlink}}GH13.html
 |}
 </div>

@@ Line 46: / Line 46: @@
 == Catalytic Residues ==
-The catalytic residues have been identified from early crystal structures <cite>Matsuura1984,Buisson1987</cite>. In fact throughout the family GH13 only the catalytic triad plus an arginine residue are totally conserved; the catalytic site includes an aspartate as [[catalytic nucleophile]], a glutamate as [[general acid/base]], and an aspartate that participates critically in stabilizing the [[transition state]] <cite>Uitdehaag1999</cite>. The fourth invariantly conserved GH13 residue, the arginine, is positioned two residues preceding the catalytic nucleophile <cite>MacGregor2001</cite>. This conservation does not apply for the enzymatically inactive heavy-chains (rBAT proteins and 4F2hc antigens) of the amino acid transporters <cite>Gabrisko2009</cite>. Numerous mutational analyses have been performed to confirm the essential roles of the three residues in catalysis, and normally the loss in activity is four-five orders of magnitude.
+The catalytic residues have been identified from early crystal structures <cite>Matsuura1984,Buisson1987</cite>. In fact throughout the family GH13 only the catalytic triad plus an arginine residue are totally conserved; the catalytic site includes an aspartate as [[catalytic nucleophile]], a glutamate as [[general acid/base]], and an aspartate that participates critically in stabilizing the [[transition state]] <cite>Uitdehaag1999</cite>. The fourth invariantly conserved GH13 residue, the arginine, is positioned two residues preceding the catalytic nucleophile <cite>MacGregor2001</cite>. This conservation does not apply for the enzymatically inactive heavy-chains (rBAT proteins and 4F2hc antigens) of the amino acid transporters <cite>Gabrisko2009</cite>. Numerous mutational analyses have been performed to confirm the essential roles of the three residues in catalysis, and normally the loss in activity is four to five orders of magnitude.
 == Three-dimensional structures ==

@@ Line 38: / Line 38: @@
 The α-amylase family was defined in 1991 as family GH13 when the sequence-based classification of glycoside hydrolases was created <cite>Henrissat1991</cite>. The α-amylase family as an enzyme family, however, was established based on results of several independent findings focused on starch hydrolases and related enzymes <cite>MacGregor1989,Jespersen1991,Jespersen1993,Takata1992</cite>. These enzymes were shown to exhibit sequence similarities and, at that time, a predicted (β/α)8-barrel (i.e. TIM-barrel) fold. The basic criteria for a protein to be a member of the α-amylase family were as follows <cite>Takata1992</cite>: the enzyme should (i) act on the α-glucosidic linkages; (ii) hydrolyse or form by transglycosylation the α-glucosidic linkages; (iii) contain the four conserved sequence regions in its amino acid sequence; and (iv) possess the catalytic triad formed by the three residues corresponding to Asp206, Glu230 and Asp297 of Taka-amylase A (the α-amylase from ''Aspergillus oryzae''). A dramatic increase of the number of GH13 members to several thousands <cite>Cantarel2009</cite> offered a greater variety in both substrate and product specificities and sequence diversity so that the above criteria had to be updated. For example, also enzymes active on α-1,1-, α-1,2-, α-1,3- and α-1,5-glucosidic linkages belong to the α-amylase family <cite>MacGregor2001</cite> and the four best known and well-accepted conserved sequence regions, defined first for eleven α-amylases <cite>Nakajima1986</cite>, were completed by the additional three regions <cite>Janecek1992,Janecek1994a</cite> which can often help to assign the correct enzyme specificity of α-amylase family members (for a review, see <cite>Janecek2002</cite>). Of note may be the enzyme neopullulanase <cite>Kuriki1991</cite> that was found to catalyze both the hydrolysis of α-1,4- and α-1,6-glucosidic bonds as well as the transglycosylation to form these two types of glucosidic bonds.
-The α-amylase family represents a clan GH-H of three glycoside hydrolase families GH13, [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>, and should be distinguished from the second smaller α-amylase family [[GH57]] <cite>Janecek2005</cite>. A remote homology to the family [[GH31]] has also been discussed <cite>Janecek2007</cite>.
+The α-amylase family represents a clan GH-H of three glycoside hydrolase families GH13, [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>, and should be distinguished from the second smaller α-amylase family [[GH57]] <cite>Janecek2005</cite>. A remote homology to the family [[GH31]] has also been discussed <cite>Janecek2007</cite>. The evolutionary relationships were described for the entire GH13 family <cite>Jespersen1993,Janecek1994b,Janecek1997a,Stam2006</cite> and some closely related specificities, i.e. subfamilies <cite>Park2000,Oslancova2002</cite>, as well as many examples of close evolutionary relatedness were reported for the individual groups of α-amylases, e.g., those from animals and actinomycetes <cite>Janecek1994a</cite>, plants and archaeons <cite>Janecek1999b,Jones1999</cite>, insects <cite>DaLage2004</cite>, and fungi <cite>vanderKaaij2007,Hostinova2010</cite>.
 Exogenous and endogenous inhibitory proteins have also been reported from microorganisms and plants <cite>Bowman1945</cite> directed towards α-amylases <cite>Svensson2004</cite> and limit dextrinases <cite>Macri1993,MacGregor2003,MacGregor2004</cite>.

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-Family GH13 is the major [[glycoside hydrolase]]  family acting on substrates containing α-glucoside linkages. A number of reviews are concerned with α-amylases <cite>Svensson1994,Janecek1997a,Kuriki1999,MacGregor2001,vanderMaarel2002</cite>. GH13 contains hydrolases, transglycosidases and isomerases <cite>MacGregor2001</cite>; noticeably animal amino acid transporters <cite>Janecek1997b</cite>, which have no glycosidase activity <cite>Fort2007</cite>, are also GH13 members. The enzymes are found in a very wide range of organisms from all kingdoms. While known specificities are indicated by the enzyme named as listed below, for several of these numerous enzymes are characterized representing subspecificities defined by structural requirements for preferred substrates or the structure of the predominant product(s). Described enzymes include: α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]); oligo-1,6-glucosidase (EC [{{EClink}}3.2.1.10 3.2.1.10]); α-glucosidase (EC [{{EClink}}3.2.1.20 3.2.1.20]); pullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]); cyclomaltodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]); maltotetraose-forming α-amylase (EC [{{EClink}}3.2.1.60 3.2.1.60]); isoamylase (EC [{{EClink}}3.2.1.68 3.2.1.68]); dextran glucosidase (EC [{{EClink}}3.2.1.70 3.2.1.70]); trehalose-6-phosphate hydrolase (EC [{{EClink}}3.2.1.93 3.2.1.93]); maltohexaose-forming α-amylase (EC [{{EClink}}3.2.1.98 3.2.1.98]); maltotriose-forming α-amylase (EC [{{EClink}}3.2.1.116 3.2.1.116]); maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]); neopullulanase (EC [{{EClink}}3.2.1.135 3.2.1.135]); malto-oligosyltrehalose trehalohydrolase (EC [{{EClink}}3.2.1.141 3.2.1.141]); maltopentaose-forming α-amylase (EC [{{EClink}}3.2.1.- 3.2.1.-]); amylosucrase (EC [{{EClink}}2.4.1.4 2.4.1.4]); sucrose phosphorylase (EC [{{EClink}}2.4.1.7 2.4.1.7]); branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]); cyclomaltodextrin glucanotransferase (CGTase) (EC [{{EClink}}2.4.1.19 2.4.1.19]); 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]); isomaltulose synthase (EC [{{EClink}}5.4.99.11 5.4.99.11]); trehalose synthase (EC [{{EClink}}5.4.99.16 5.4.99.16]). As mentioned above, heavy-chains of heteromeric amino acid transporters belong to the GH13 <cite>Janecek1997b,Gabrisko2009</cite>. Among thousands of sequences and ~30 different enzymes specificities <cite>Cantarel2009</cite> many are closely related to each other, GH13 therefore has officially been subdivided into almost 40 subfamilies <cite>Stam2006</cite>; several subfamilies, e.g., the oligo-1,6-glucosidase and neopullulanase subfamilies were described earlier <cite>Oslancova2002</cite>. Noticeably a considerable number of GH13 members contain carbohydrate binding modules (CBMs) referred to as starch binding domains belonging to CBM20, 21, 25, 26, 34, 41, 45, 48, 53, and 58 <cite>Svensson1989,Janecek1999a,Rodriguez-Sanoja2005,Machovic2006,Christiansen2009</cite>.
+Family GH13 is the major [[glycoside hydrolase]]  family acting on substrates containing α-glucoside linkages. A number of reviews are concerned with α-amylases <cite>Svensson1994,Janecek1997a,Kuriki1999,MacGregor2001,vanderMaarel2002</cite>. GH13 contains hydrolases, transglycosidases and isomerases <cite>MacGregor2001</cite>; noticeably animal amino acid transporters <cite>Janecek1997b</cite>, which have no glycosidase activity <cite>Fort2007</cite>, are also GH13 members. The enzymes are found in a very wide range of organisms from all kingdoms. While known specificities are indicated by the enzyme named as listed below, for several of these numerous enzymes are characterized representing subspecificities defined by structural requirements for preferred substrates or the structure of the predominant product(s).
 The GH13 enzymes have a wide range of different preferred substrates and products. For example, the α-amylases prefer polysaccharides of the α-1,4-glucan type, such as amylose and amylopectin, but are also able to attack the supramolecular structures represented by starch granules and glycogen particles. Besides they have some significant albeit slower turn-over of maltooligosaccharides of a certain degree of polymerization. These typical substrate profiles can be manipulated through protein engineering.