DB code: D00243

CATH domain 3.40.50.1170 : Rossmann fold Catalytic domain
3.40.50.40 : Rossmann fold Catalytic domain
E.C. 3.5.1.38
CSA 1djo
M-CSA 1djo
MACiE M0029

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P10172 Glutaminase-asparaginase
EC 3.5.1.38
L-ASNase/L-GLNase
L-asparagine/L-glutamine amidohydrolase
PF00710 (Asparaginase)
[Graphical View]
P10182 Glutaminase-asparaginase
EC 3.5.1.38
L-ASNase/L-GLNase
L-asparagine/L-glutamine amidohydrolase
PGA
PF00710 (Asparaginase)
[Graphical View]

KEGG enzyme name
glutamin-(asparagin-)ase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10172 ASPQ_ACIGL L-glutamine + H(2)O = L-glutamate + NH(3). L-asparagine + H(2)O = L-aspartate + NH(3). Homotetramer. Periplasm (By similarity).
P10182 ASPQ_PSES7 L-glutamine + H(2)O = L-glutamate + NH(3). L-asparagine + H(2)O = L-aspartate + NH(3). Homotetramer. Periplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00251 Glutamate metabolism
MAP00252 Alanine and aspartate metabolism
MAP00471 D-Glutamine and D-glutamate metabolism
MAP00910 Nitrogen metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00064 C00152 C00001 C00025 C00049 C00014
E.C.
Compound L-Glutamine L-Asparagine H2O L-Glutamate L-Aspartate NH3
Type amino acids,amide group amino acids,amide group H2O amino acids,carboxyl group amino acids,carboxyl group amine group,organic ion
ChEBI 18050
 58359
 18050
 58359
 		17196
 58048
 17196
 58048
 		15377
 15377
 		16015
 16015
 		17053
 17053
 		16134
 16134
PubChem 5961
 6992086
 5961
 6992086
 		6267
 6992089
 6267
 6992089
 		22247451
 962
 22247451
 962
 		33032
 44272391
 88747398
 33032
 44272391
 88747398
 		44367445
 5960
 44367445
 5960
 		222
 222
1agxA01 Unbound Unbound Unbound Unbound Unbound Unbound
1djoA01 Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:CAB
1djoB01 Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:CAB
1djpA01 Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:DO2
1djpB01 Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:DO2
3pga101 Unbound Unbound Unbound Unbound Unbound Unbound
3pga201 Unbound Unbound Unbound Unbound Unbound Unbound
3pga301 Unbound Unbound Unbound Unbound Unbound Unbound
3pga401 Unbound Unbound Unbound Unbound Unbound Unbound
4pgaA01 Unbound Unbound Unbound Analogue:SO4-NH4 Unbound Unbound
4pgaB01 Unbound Unbound Unbound Analogue:SO4-NH4 Unbound Unbound
1agxA02 Unbound Unbound Unbound Unbound Unbound Unbound
1djoA02 Unbound Unbound Unbound Unbound Unbound Unbound
1djoB02 Unbound Unbound Unbound Unbound Unbound Unbound
1djpA02 Unbound Unbound Unbound Unbound Unbound Unbound
1djpB02 Unbound Unbound Unbound Unbound Unbound Unbound
3pga102 Unbound Unbound Unbound Unbound Unbound Unbound
3pga202 Unbound Unbound Unbound Unbound Unbound Unbound
3pga302 Unbound Unbound Unbound Unbound Unbound Unbound
3pga402 Unbound Unbound Unbound Unbound Unbound Unbound
4pgaA02 Unbound Unbound Unbound Unbound Unbound Unbound
4pgaB02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;3pga,4pga & Swiss-prot;P10172,P10182 & Leterature [7],[10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1agxA01 THR 12;TYR 26;THR 92;ASP 93;LYS 165
1djoA01 THR 1020;TYR 1034;THR 1100;ASP 1101;LYS 1173
1djoB01 THR 3020;TYR 3034;THR 3100;ASP 3101;LYS 3173
1djpA01 THR 1020;TYR 1034;THR 1100;ASP 1101;LYS 1173
1djpB01 THR 3020;TYR 3034;THR 3100;ASP 3101;LYS 3173
3pga101 THR 20;TYR 34;THR 100;ASP 101;LYS 173
3pga201 THR 20;TYR 34;THR 100;ASP 101;LYS 173
3pga301 THR 20;TYR 34;THR 100;ASP 101;LYS 173
3pga401 THR 20;TYR 34;THR 100;ASP 101;LYS 173
4pgaA01 THR 20;TYR 34;THR 100;ASP 101;LYS 173
4pgaB01 THR 20;TYR 34;THR 100;ASP 101;LYS 173
1agxA02 GLU 288
1djoA02 GLU 1294
1djoB02 GLU 3294
1djpA02 GLU 1294
1djpB02 GLU 3294
3pga102 GLU 294
3pga202 GLU 294
3pga302 GLU 294
3pga402 GLU 294
4pgaA02 GLU 294
4pgaB02 GLU 294

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
p.831-832
[8]
p.10262-10264
[9]
p.928-930
[10]
Scheme 3, p.1203-1204

References
[1]
Resource
Comments
Medline ID
PubMed ID 5017769
Journal J Biol Chem
Year 1972
Volume 247
Pages 84-90
Authors Roberts J, Holcenberg JS, Dolowy WC
Title Isolation, crystallization, and properties of Achromobacteraceae glutaminase-asparaginase with antitumor activity.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 5441
Journal J Biol Chem
Year 1976
Volume 251
Pages 2119-23
Authors Roberts J
Title Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7Z.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 875029
Journal J Mol Biol
Year 1977
Volume 112
Pages 515-9
Authors Wlodawer A, Roberts J, Holcenberg JS
Title Characterization of crystals of L-glutaminase-asparaginase from Acinetobacter glutaminasificans and Pseudomonas 7A.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 619999
Journal Biochemistry
Year 1978
Volume 17
Pages 411-7
Authors Holcenberg JS, Ericsson L, Roberts J
Title Amino acid sequence of the diazooxonorleucine binding site of Acinetobacter and Pseudomonas 7A glutaminase--asparaginase enzymes.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3275637
Journal J Biol Chem
Year 1988
Volume 263
Pages 150-6
Authors Ammon HL, Weber IT, Wlodawer A, Harrison RW, Gilliland GL, Murphy KC, Sjolin L, Roberts J
Title Preliminary crystal structure of Acinetobacter glutaminasificans glutaminase-asparaginase.
Related PDB
Related UniProtKB
[6]
Resource
Comments PROTEIN SEQUENCE
Medline ID
PubMed ID 3379033
Journal J Biol Chem
Year 1988
Volume 263
Pages 8583-91
Authors Tanaka S, Robinson EA, Appella E, Miller M, Ammon HL, Roberts J, Weber IT, Wlodawer A
Title Structures of amidohydrolases. Amino acid sequence of a glutaminase-asparaginase from Acinetobacter glutaminasificans and preliminary crystallographic data for an asparaginase from Erwinia chrysanthemi.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS)
Medline ID
PubMed ID 15299349
Journal Acta Crystallogr D Biol Crystallogr
Year 1994
Volume 50
Pages 826-32
Authors Lubkowski J, Wlodawer A, Housset D, Weber IT, Ammon HL, Murphy KC, Swain AL
Title Refined crystal structure of Acinetobacter glutaminasificans glutaminase-asparaginase.
Related PDB 1agx
Related UniProtKB P10172
[8]
Resource
Comments PROTEIN SEQUENCE, AND X-ray crystallography (2.0 ANGSTROMS)
Medline ID
PubMed ID 8068664
Journal Biochemistry
Year 1994
Volume 33
Pages 10257-65
Authors Lubkowski J, Wlodawer A, Ammon HL, Copeland TD, Swain AL
Title Structural characterization of Pseudomonas 7A glutaminase-asparaginase.
Related PDB 3pga
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS)
Medline ID 9020792
PubMed ID 9020792
Journal Biochemistry
Year 1997
Volume 36
Pages 923-31
Authors Jakob CG, Lewinski K, LaCount MW, Roberts J, Lebioda L
Title Ion binding induces closed conformation in Pseudomonas 7A glutaminase-asparaginase (PGA): crystal structure of the PGA-SO4(2-)-NH4+ complex at 1.7 A resolution.
Related PDB 4pga
Related UniProtKB P10182
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10684596
Journal Biochemistry
Year 2000
Volume 39
Pages 1199-204
Authors Ortlund E, Lacount MW, Lewinski K, Lebioda L
Title Reactions of Pseudomonas 7A glutaminase-asparaginase with diazo analogues of glutamine and asparagine result in unexpected covalent inhibitions and suggests an unusual catalytic triad Thr-Tyr-Glu.
Related PDB 1djo 1djp
Related UniProtKB

Comments
This enzyme catalyzes hydrolysis of amide bond.
According to the literature [10], Thr20 (of 3pga) acts as a nuclephile, whereas there are two sets of acid-base/modulator, Tyr34/Glu294' (from the adjacent subunit) and Lys173/Asp101. (Thr100 might be a proton shuttle.)

Created Updated
2004-03-24 2009-02-26