DB code: D00169

RLCP classification	1.30.36010.970 : Hydrolysis
CATH domain	2.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A)
CATH domain	3.20.20.80 : TIM Barrel	Catalytic domain
E.C.	3.2.1.8
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
2.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A)	D00666 M00185
3.20.20.80 : TIM Barrel	S00202 S00210 S00748 S00906 S00907 S00911 S00912 S00915 M00134 M00160 D00479 S00204 S00205 S00206 S00207 S00203 S00208 S00209 S00211 S00213 S00214 M00113 T00307 D00165 D00166 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
P26514	Endo-1,4-beta-xylanase A	Xylanase A EC 3.2.1.8 1,4-beta-D-xylan xylanohydrolase A	CBM13 (Carbohydrate-Binding Module Family 13) GH10 (Glycoside Hydrolase Family 10)	PF00331 (Glyco_hydro_10) PF00652 (Ricin_B_lectin) [Graphical View]
Q7SI98		Hydrolase	CBM13 (Carbohydrate-Binding Module Family 13) GH10 (Glycoside Hydrolase Family 10)	PF00331 (Glyco_hydro_10) PF00652 (Ricin_B_lectin) [Graphical View]

KEGG enzyme name
endo-1,4-beta-xylanase endo-(1->4)-beta-xylan 4-xylanohydrolase endo-1,4-xylanase xylanase beta-1,4-xylanase endo-1,4-xylanase endo-beta-1,4-xylanase endo-1,4-beta-D-xylanase 1,4-beta-xylan xylanohydrolase beta-xylanase beta-1,4-xylan xylanohydrolase endo-1,4-beta-xylanase beta-D-xylanase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P26514	XYNA_STRLI	Endohydrolysis of (1->4)-beta-D-xylosidic linkages in xylans.		Secreted.
Q7SI98	Q7SI98_STROI

KEGG Pathways
Map code	Pathways	E.C.

Compound table
	Substrates		Products		Intermediates
KEGG-id	C00707	C00001	C00707	C00707
E.C.
Compound	Xylan	H2O	Xylan	Xylan
Type	polysaccharide	H2O	polysaccharide	polysaccharide
ChEBI		15377 15377
PubChem		22247451 962 22247451 962

1xyfA01	Unbound		Unbound	Unbound	Unbound
1xyfB01	Unbound		Unbound	Unbound	Unbound
1isvA01	Unbound		Unbound	Unbound	Unbound
1isvB01	Unbound		Unbound	Unbound	Unbound
1iswA01	Unbound		Unbound	Unbound	Unbound
1iswB01	Unbound		Unbound	Unbound	Unbound
1isxA01	Unbound		Unbound	Unbound	Unbound
1isxB01	Unbound		Unbound	Unbound	Unbound
1isyA01	Unbound		Unbound	Unbound	Unbound
1isyB01	Unbound		Unbound	Unbound	Unbound
1iszA01	Unbound		Unbound	Unbound	Unbound
1iszB01	Unbound		Unbound	Unbound	Unbound
1it0A01	Unbound		Unbound	Unbound	Unbound
1it0B01	Unbound		Unbound	Unbound	Unbound
1knlA	Unbound		Unbound	Unbound	Unbound
1knmA	Unbound		Unbound	Unbound	Unbound
1mc9A	Unbound		Unbound	Unbound	Unbound
1xyfA02	Unbound		Unbound	Unbound	Unbound
1xyfB02	Unbound		Unbound	Unbound	Unbound
1isvA02	Unbound		Unbound	Unbound	Unbound
1isvB02	Unbound		Unbound	Unbound	Unbound
1iswA02	Unbound		Bound:XYP-XYP(chain C)	Bound:XYP-XYP(chain D)	Unbound
1iswB02	Unbound		Bound:XYP-XYP(chain F)	Bound:XYP-XYP(chain G)	Unbound
1isxA02	Unbound		Bound:XYP-XYP-XYP(chain C)	Bound:XYP-XYP(chain D)	Unbound
1isxB02	Unbound		Bound:XYP-XYP-XYP(chain F)	Bound:XYP-XYP-XYP(chain G)	Unbound
1isyA02	Unbound		Unbound	Unbound	Unbound
1isyB02	Unbound		Unbound	Unbound	Unbound
1iszA02	Unbound		Unbound	Unbound	Unbound
1iszB02	Unbound		Unbound	Unbound	Unbound
1it0A02	Unbound		Unbound	Unbound	Unbound
1it0B02	Unbound		Unbound	Unbound	Unbound
1e0vA	Unbound		Unbound	Unbound	Intermediate-analogue:FFC
1e0wA	Unbound		Unbound	Unbound	Unbound
1e0xA	Unbound		Unbound	Unbound	Intermediate-analogue:XYP-X2F
1e0xB	Unbound		Unbound	Unbound	Intermediate-analogue:XYP-X2F
1od8A	Unbound		Analogue:XYP-XDL	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
PDB;1xyf, Swiss-prot;P26514

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

1xyfA01
1xyfB01
1isvA01
1isvB01
1iswA01
1iswB01
1isxA01
1isxB01
1isyA01
1isyB01
1iszA01
1iszB01
1it0A01
1it0B01
1knlA
1knmA
1mc9A
1xyfA02	GLU 128;HIS 207;GLU 236;ASP 238
1xyfB02	GLU 628;HIS 707;GLU 736;ASP 738
1isvA02	GLU 128;HIS 207;GLU 236;ASP 238
1isvB02	GLU 628;HIS 707;GLU 736;ASP 738
1iswA02	GLU 128;HIS 207;GLU 236;ASP 238
1iswB02	GLU 628;HIS 707;GLU 736;ASP 738
1isxA02	GLU 128;HIS 207;GLU 236;ASP 238
1isxB02	GLU 628;HIS 707;GLU 736;ASP 738
1isyA02	GLU 128;HIS 207;GLU 236;ASP 238
1isyB02	GLU 628;HIS 707;GLU 736;ASP 738
1iszA02	GLU 128;HIS 207;GLU 236;ASP 238
1iszB02	GLU 628;HIS 707;GLU 736;ASP 738
1it0A02	GLU 128;HIS 207;GLU 236;ASP 238
1it0B02	GLU 628;HIS 707;GLU 736;ASP 738
1e0vA	GLU 128;HIS 207;GLU 236;ASP 238
1e0wA	GLU 128;HIS 207;GLU 236;ASP 238
1e0xA	GLU 128;HIS 207;GLU 236;ASP 238
1e0xB	GLU 128;HIS 207;GLU 236;ASP 238
1od8A	GLU 128;HIS 207;GLU 236;ASP 238

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[7]
[11]	Fig.4
[12]	p.20813
[19]
[20]
[22]	Fig.1	4

References
[1]
Resource
Comments
Medline ID
PubMed ID	3141761
Journal	Microbiol Rev
Year	1988
Volume	52
Pages	305-17
Authors	Wong KK, Tan LU, Saddler JN
Title	Multiplicity of beta-1,4-xylanase in microorganisms: functions and applications.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	1368510
Journal	Agric Biol Chem
Year	1990
Volume	54
Pages	449-57
Authors	Yoshida S, Kusakabe I, Matsuo N, Shimizu K, Yasui T, Murakami K
Title	Structure of rice-straw arabinoglucuronoxylan and specificity of Streptomyces xylanase toward the xylan.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	1761039
Journal	Eur J Biochem
Year	1991
Volume	202
Pages	367-77
Authors	Gilkes NR, Claeyssens M, Aebersold R, Henrissat B, Meinke A, Morrison HD, Kilburn DG, Warren RA, Miller RC Jr
Title	Structural and functional relationships in two families of beta-1,4-glycanases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	1886523
Journal	Microbiol Rev
Year	1991
Volume	55
Pages	303-15
Authors	Gilkes NR, Henrissat B, Kilburn DG, Miller RC Jr, Warren RA
Title	Domains in microbial beta-1, 4-glycanases: sequence conservation, function, and enzyme families.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	8457588
Journal	Biochim Biophys Acta
Year	1993
Volume	1162
Pages	246-54
Authors	Biely P, Kluepfel D, Morosoli R, Shareck F
Title	Mode of action of three endo-beta-1,4-xylanases of Streptomyces lividans.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	8471845
Journal	Protein Expr Purif
Year	1993
Volume	4
Pages	120-9
Authors	Grabski AC, Forrester IT, Patel R, Jeffries TW
Title	Characterization and N-terminal amino acid sequences of beta-(1-4)endoxylanases from Streptomyces roseiscleroticus: purification incorporating a bioprocessing agent.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	7915112
Journal	Biochem J
Year	1994
Volume	302
Pages	291-5
Authors	Moreau A, Roberge M, Manin C, Shareck F, Kluepfel D, Morosoli R
Title	Identification of two acidic residues involved in the catalysis of xylanase A from Streptomyces lividans.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	7765032
Journal	Biosci Biotechnol Biochem
Year	1994
Volume	58
Pages	1041-4
Authors	Yoshida S, Satoh T, Shimokawa S, Oku T, Ito T, Kusakabe I
Title	Substrate specificity of Streptomyces beta-xylanase toward glucoxylan.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	8000329
Journal	Braz J Med Biol Res
Year	1994
Volume	27
Pages	1093-109
Authors	Ferreira-Filho EX
Title	The xylan-degrading enzyme system.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	7764794
Journal	Enzyme Microb Technol
Year	1994
Volume	16
Pages	420-4
Authors	Moreau A, Shareck F, Kluepfel D, Morosoli R
Title	Increase in catalytic activity and thermostability of the xylanase A of Streptomyces lividans 1326 by site-specific mutagenesis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	8306993
Journal	Eur J Biochem
Year	1994
Volume	219
Pages	261-6
Authors	Moreau A, Shareck F, Kluepfel D, Morosoli R
Title	Alteration of the cleavage mode and of the transglycosylation reactions of the xylanase A of Streptomyces lividans 1326 by site-directed mutagenesis of the Asn173 residue.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	8063693
Journal	J Biol Chem
Year	1994
Volume	269
Pages	20811-4
Authors	Derewenda U, Swenson L, Green R, Wei Y, Morosoli R, Shareck F, Kluepfel D, Derewenda ZS
Title	Crystal structure, at 2.6-A resolution, of the Streptomyces lividans xylanase A, a member of the F family of beta-1,4-D-glycanases.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	7729513
Journal	FEBS Lett
Year	1995
Volume	362
Pages	281-5
Authors	Jenkins J, Lo Leggio L, Harris G, Pickersgill R
Title	Beta-glucosidase, beta-galactosidase, family A cellulases, family F xylanases and two barley glycanases form a superfamily of enzymes with 8-fold beta/alpha architecture and with two conserved glutamates near the carboxy-terminal ends of beta-strands four and seven.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID	9201919
Journal	Biochemistry
Year	1997
Volume	36
Pages	7769-75
Authors	Roberge M, Shareck F, Morosoli R, Kluepfel D, Dupont C
Title	Characterization of two important histidine residues in the active site of xylanase A from Streptomyces lividans, a family 10 glycanase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID	9118232
Journal	Crit Rev Biotechnol
Year	1997
Volume	17
Pages	39-67
Authors	Sunna A, Antranikian G
Title	Xylanolytic enzymes from fungi and bacteria.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID	9006940
Journal	J Biol Chem
Year	1997
Volume	272
Pages	2942-51
Authors	Charnock SJ, Lakey JH, Virden R, Hughes N, Sinnott ML, Hazlewood GP, Pickersgill R, Gilbert HJ
Title	Key residues in subsite F play a critical role in the activity of Pseudomonas fluorescens subspecies cellulosa xylanase A against xylooligosaccharides but not against highly polymeric substrates such as xylan.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID	9211898
Journal	J Biol Chem
Year	1997
Volume	272
Pages	17523-30
Authors	Spurway TD, Morland C, Cooper A, Sumner I, Hazlewood GP, O'Donnell AG, Pickersgill RW, Gilbert HJ
Title	Calcium protects a mesophilic xylanase from proteinase inactivation and thermal unfolding.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID	9335171
Journal	J Biotechnol
Year	1997
Volume	57
Pages	151-66
Authors	Biely P, Vrsanska M, Tenkanen M, Kluepfel D
Title	Endo-beta-1,4-xylanase families: differences in catalytic properties.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID	9194164
Journal	Protein Eng
Year	1997
Volume	10
Pages	399-403
Authors	Roberge M, Dupont C, Morosoli R, Shareck F, Kluepfel D
Title	Asparagine-127 of xylanase A from Streptomyces lividans, a key residue in glycosyl hydrolases of superfamily 4/7: kinetic evidence for its involvement in stabilization of the catalytic intermediate.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID	9681873
Journal	Protein Eng
Year	1998
Volume	11
Pages	399-404
Authors	Roberge M, Shareck F, Morosoli R, Kluepfel D, Dupont C
Title	Site-directed mutagenesis study of a conserved residue in family 10 glycanases: histidine 86 of xylanase A from Streptomyces lividans.
Related PDB
Related UniProtKB
[21]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID
PubMed ID	10571062
Journal	FEBS Lett
Year	1999
Volume	460
Pages	61-6
Authors	Kaneko S, Kuno A, Fujimoto Z, Shimizu D, Machida S, Sato Y, Yura K, Go M, Mizuno H, Taira K, Kusakabe I, Hayashi K
Title	An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivaceoviridis E-86 by module shuffling with the Cex of Cellulomonas fimi and by site-directed mutagenesis.
Related PDB	1xyf
Related UniProtKB	Q7SI98
[22]
Resource
Comments
Medline ID
PubMed ID	10359093
Journal	FEBS Lett
Year	1999
Volume	450
Pages	299-305
Authors	Kuno A, Shimizu D, Kaneko S, Hasegawa T, Gama Y, Hayashi K, Kusakabe I, Taira K
Title	Significant enhancement in the binding of p-nitrophenyl-beta-D-xylobioside by the E128H mutant F/10 xylanase from Streptomyces olivaceoviridis E-86.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID	10570988
Journal	Gene
Year	1999
Volume	238
Pages	93-101
Authors	Sato Y, Niimura Y, Yura K, Go M
Title	Module-intron correlation and intron sliding in family F/10 xylanase genes.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID	10235626
Journal	Protein Eng
Year	1999
Volume	12
Pages	251-7
Authors	Roberge M, Shareck F, Morosoli R, Kluepfel D, Dupont C
Title	Characterization of active-site aromatic residues in xylanase A from Streptomyces lividans.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID	10884353
Journal	J Mol Biol
Year	2000
Volume	300
Pages	575-85
Authors	Fujimoto Z, Kuno A, Kaneko S, Yoshida S, Kobayashi H, Kusakabe I, Mizuno H
Title	Crystal structure of Streptomyces olivaceoviridis E-86 beta-xylanase containing xylan-binding domain.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID	10767281
Journal	J Biol Chem
Year	2000
Volume	275
Pages	23027-33
Authors	Andrews SR, Charnock SJ, Lakey JH, Davies GJ, Claeyssens M, Nerinckx W, Underwood M, Sinnott ML, Warren RA, Gilbert HJ
Title	Substrate specificity in glycoside hydrolase family 10. Tyrosine 87 and leucine 314 play a pivotal role in discriminating between glucose and xylose binding in the proximal active site of Pseudomonas cellulosa xylanase 10A.
Related PDB	1e0v 1e0w 1e0x
Related UniProtKB
[27]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID
PubMed ID	11829503
Journal	J Mol Biol
Year	2002
Volume	316
Pages	65-78
Authors	Fujimoto Z, Kuno A, Kaneko S, Kobayashi H, Kusakabe I, Mizuno H
Title	Crystal structures of the sugar complexes of Streptomyces olivaceoviridis E-86 xylanase: sugar binding structure of the family 13 carbohydrate binding module.
Related PDB	1isv 1isw 1isx 1isy 1isz 1it0
Related UniProtKB	Q7SI98
[28]
Resource
Comments
Medline ID
PubMed ID	11914070
Journal	Biochemistry
Year	2002
Volume	41
Pages	4246-54
Authors	Notenboom V, Boraston AB, Williams SJ, Kilburn DG, Rose DR
Title	High-resolution crystal structures of the lectin-like xylan binding domain from Streptomyces lividans xylanase 10A with bound substrates reveal a novel mode of xylan binding.
Related PDB	1knl 1knm 1mc9
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID	12744311
Journal	Chem Commun (Camb)
Year	2003
Volume
Pages	944-5
Authors	Gloster T, Williams SJ, Tarling CA, Roberts S, Dupont C, Jodoin P, Shareck F, Withers SG, Davies GJ
Title	A xylobiose-derived isofagomine lactam glycosidase inhibitor binds as its amide tautomer.
Related PDB	1od8
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID	15078885
Journal	J Biol Chem
Year	2004
Volume	279
Pages	26619-26
Authors	Kaneko S, Ichinose H, Fujimoto Z, Kuno A, Yura K, Go M, Mizuno H, Kusakabe I, Kobayashi H
Title	Structure and function of a family 10 beta-xylanase chimera of Streptomyces olivaceoviridis E-86 FXYN and Cellulomonas fimi Cex.
Related PDB
Related UniProtKB

Comments
This family belongs to the glycosidase family-10, which has a retaining mechanism (equatorial to equatorial conformation), and also a family of 4/7 superfamily, which has got catalytic residues at the C-terminal ends of beta-4 and beta-7 on the (alpha/beta)8 barrel fold. According to the literature [22], Glu236 and Glu128 (of 1ece) act as a nucleophile and acid-base, respectively. The catalysis proceeds through a dissociative-type (or SN1-like) mechanism, with a formation of oxocarbonium ion in the transition state, during the glycosylation of the active site. During the glycosylation, Glu236 approaches the C1 atom of xylan substrate, whilst Glu128 protonates the leaving sugar group. At the second stage, or during the deglycosylation, a water molecule can be activated by a general base, Glu128. This deglycosylation also goes through the dissociative-type reaction with an oxocarbonium ion in the transition state, in which water replaced the xylan leaving group in the first step. According to the paper [19], the conserved residue at active site, Asn127, may stabilize the intermediate or transition state. Meanwhile, the paper [20] mentioned that His86 might modulate the acid-base catalyst (Glu128), by maintaining the elevated pKa of the catalytic residue. Moreover, comparing the structural data with that of the other family-10 enzyme, xylanase (E.C. 3.2.1.8) (D00479 in EzCatDB), His207-Asp238 dyad seems to stabilize the leaving nucleophile, Glu236, during the deglycosylation.

Comments

This family belongs to the glycosidase family-10, which has a retaining mechanism (equatorial to equatorial conformation), and also a family of 4/7 superfamily, which has got catalytic residues at the C-terminal ends of beta-4 and beta-7 on the (alpha/beta)8 barrel fold.
According to the literature [22], Glu236 and Glu128 (of 1ece) act as a nucleophile and acid-base, respectively. The catalysis proceeds through a dissociative-type (or SN1-like) mechanism, with a formation of oxocarbonium ion in the transition state, during the glycosylation of the active site.
During the glycosylation, Glu236 approaches the C1 atom of xylan substrate, whilst Glu128 protonates the leaving sugar group.
At the second stage, or during the deglycosylation, a water molecule can be activated by a general base, Glu128. This deglycosylation also goes through the dissociative-type reaction with an oxocarbonium ion in the transition state, in which water replaced the xylan leaving group in the first step.
According to the paper [19], the conserved residue at active site, Asn127, may stabilize the intermediate or transition state. Meanwhile, the paper [20] mentioned that His86 might modulate the acid-base catalyst (Glu128), by maintaining the elevated pKa of the catalytic residue.
Moreover, comparing the structural data with that of the other family-10 enzyme, xylanase (E.C. 3.2.1.8) (D00479 in EzCatDB), His207-Asp238 dyad seems to stabilize the leaving nucleophile, Glu236, during the deglycosylation.

Created	Updated
2004-08-19	2009-02-26