DB code: T00002

CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 Catalytic domain
1.20.5.320 : Single alpha-helices involved in coiled-coils or other helix-helix interfaces
E.C. 1.1.1.44
CSA 2pgd
M-CSA 2pgd
MACiE

CATH domain Related DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 D00007 D00012 D00603 T00227
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P31072 6-phosphogluconate dehydrogenase, decarboxylating
EC 1.1.1.44
PF00393 (6PGD)
PF03446 (NAD_binding_2)
[Graphical View]
P00349 6-phosphogluconate dehydrogenase, decarboxylating
EC 1.1.1.44
PF00393 (6PGD)
PF03446 (NAD_binding_2)
[Graphical View] 		NP_001009467.1 (Protein)
NM_001009467.2 (DNA/RNA sequence)

KEGG enzyme name
phosphogluconate dehydrogenase (decarboxylating)
phosphogluconic acid dehydrogenase
6-phosphogluconic dehydrogenase
6-phosphogluconic carboxylase
6-phosphogluconate dehydrogenase (decarboxylating)
6-phospho-D-gluconate dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P31072 6PGD_TRYBB 6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO(2) + NADPH. Homodimer.
P00349 6PGD_SHEEP 6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO(2) + NADPH. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00030 Pentose phosphate pathway
MAP00480 Glutathione metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00003 C00006 C00345 C00004 C00005 C00199 C00011 C00080
E.C.
Compound NAD+ NADP+ 6-Phospho-D-gluconate NADH NADPH D-Ribulose 5-phosphate CO2 H+
Type amide group,amine group,nucleotide amide group,amine group,nucleotide carbohydrate,carboxyl group,phosphate group/phosphate ion amide group,amine group,nucleotide amide group,amine group,nucleotide carbohydrate,phosphate group/phosphate ion others others
ChEBI 15846
 15846
 		18009
 18009
 		48928
 48928
 		16908
 16908
 		16474
 16474
 		17363
 17363
 		16526
 16526
 		15378
 15378
PubChem 5893
 5893
 		5886
 5886
 		91493
 91493
 		439153
 439153
 		5884
 5884
 		439184
 439184
 		280
 280
 		1038
 1038
1pgjA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgjB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgdA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgnA01 Unbound Analogue:NBP Unbound Unbound Unbound Unbound Unbound
1pgoA01 Unbound Unbound Unbound Bound:NDP Unbound Unbound Unbound
1pgpA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2pgdA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgjA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgjB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgdA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgnA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgoA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgpA02 Unbound Unbound Bound:6PG Unbound Unbound Unbound Unbound
2pgdA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgjA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgjB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgdA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgnA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgoA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pgpA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2pgdA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1pgd & literature [14], [16], [18], [21], [24]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1pgjA01
1pgjB01
1pgdA01
1pgnA01
1pgoA01
1pgpA01
2pgdA01
1pgjA02 LYS 185;ASN 189;GLU 192
1pgjB02 LYS 185;ASN 189;GLU 192
1pgdA02 LYS 183;ASN 187;GLU 190
1pgnA02 LYS 183;ASN 187;GLU 190
1pgoA02 LYS 183;ASN 187;GLU 190
1pgpA02 LYS 183;ASN 187;GLU 190
2pgdA02 LYS 183;ASN 187;GLU 190
1pgjA03
1pgjB03
1pgdA03
1pgnA03
1pgoA03
1pgpA03
2pgdA03

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[14]
Fig.14, p.661-665
[17]
SCHEME 1, Fig. 5, p.219-222
[18]
p.265-266
[21]
Scheme 1, p.15697
[22]
Fig.1
[24]
p.11237
[30]
p.1210-1211
[31]
Fig.1, Fig.2, p.3427
[33]
Fig.2, p.2644-2647

References
[1]
Resource
Comments
Medline ID
PubMed ID 4773872
Journal Eur J Biochem
Year 1973
Volume 38
Pages 229-38
Authors Silverberg M, Dalziel K
Title Crystalline 6-phosphogluconate dehydrogenase from sheep liver.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 4772689
Journal FEBS Lett
Year 1973
Volume 38
Pages 49-52
Authors Pearse BM, Harris JJ
Title 6-Phosphogluconate dehydrogenase from Bacillus stearothermophilus.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 236441
Journal Methods Enzymol
Year 1975
Volume 41
Pages 214-20
Authors Silverberg M, Dalziel K
Title 6-Phospho-D-gluconate dehydrogenase from sheep liver.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 875016
Journal J Mol Biol
Year 1977
Volume 112
Pages 183-97
Authors Adams MJ, Helliwell JR, Bugg CE
Title Sturucture of 6-phosphogluconate dehydrogenase from sheep liver at 6 A resolution.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 38116
Journal Eur J Biochem
Year 1979
Volume 98
Pages 121-30
Authors Abdallah MA, Adams MJ, Archibald IG, Biellmann JF, Helliwell JR, Jenkins SE
Title Binding of coenzyme and substrate and coenzyme analogues to 6-phosphogluconate dehydrogenase from sheep liver. An X-ray study at 0.6 nm resolution.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7194116
Journal Biochim Biophys Acta
Year 1981
Volume 657
Pages 232-42
Authors Minchiotti L, Ronchi S, Rippa M
Title Amino acid sequence around the pyridoxal 5'-phosphate binding sites of 6-phosphogluconate dehydrogenase.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID 84057760
PubMed ID 6641716
Journal EMBO J
Year 1983
Volume 2
Pages 1009-14
Authors Adams MJ, Archibald IG, Bugg CE, Carne A, Gover S, Helliwell JR, Pickersgill RW, White SW
Title The three dimensional structure of sheep liver 6-phosphogluconate dehydrogenase at 2.6 A resolution.
Related PDB
Related UniProtKB P00349
[8]
Resource
Comments
Medline ID
PubMed ID 3699023
Journal Eur J Biochem
Year 1986
Volume 156
Pages 555-67
Authors Topham CM, Matthews B, Dalziel K
Title Kinetic studies of 6-phosphogluconate dehydrogenase from sheep liver.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 3581436
Journal Cell Biochem Funct
Year 1987
Volume 5
Pages 79-95
Authors Rosemeyer MA
Title The biochemistry of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glutathione reductase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 2167091
Journal Biochem Int
Year 1990
Volume 21
Pages 85-95
Authors Umazume K, Nishida M, Sakurai H, Yoshimura Y, Kawada J
Title Variations in manganese effect on 6-phosphogluconate dehydrogenases from the thyroid and liver of the mouse and an evidence for non-interchangeability of manganese and magnesium.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID 92172317
PubMed ID 1793548
Journal Acta Crystallogr B
Year 1991
Volume 47
Pages 817-20
Authors Adams MJ, Gover S, Leaback R, Phillips C, Somers DO
Title The structure of 6-phosphogluconate dehydrogenase refined at 2.5 A resolution.
Related PDB 1pgd 2pgd
Related UniProtKB P00349
[12]
Resource
Comments
Medline ID
PubMed ID 1645186
Journal Biochemistry
Year 1991
Volume 30
Pages 4970-7
Authors Knight WB, Sem DS, Smith K, Miziorko HM, Rendina AR, Cleland WW
Title Phosphorylated thiosugars: synthesis, properties, and reactivity in enzymatic reactions.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 1827991
Journal Biochemistry
Year 1991
Volume 30
Pages 4978-84
Authors Sem DS, Cleland WW
Title Phosphorylated aminosugars: synthesis, properties, and reactivity in enzymatic reactions.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS)
Medline ID 95006333
PubMed ID 7922042
Journal Structure
Year 1994
Volume 2
Pages 651-68
Authors Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C
Title Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism.
Related PDB 1pgn 1pgo 1pgp
Related UniProtKB P00349
[15]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID
PubMed ID
Journal Acta Crystallogr D Biol Crystallogr
Year 1995
Volume 51
Pages 290-304
Authors Phillips C, Gover S, Adams MJ
Title Structure of 6-phosphogluconate dehydrogenase refined at 2 angstroms resolution.
Related PDB
Related UniProtKB P00349
[16]
Resource
Comments
Medline ID
PubMed ID 8589652
Journal Biochem Mol Biol Int
Year 1995
Volume 37
Pages 785-93
Authors Hanau S, Bertelli M, Dallocchio F, Rippa M
Title Bromopyruvate for the affinity labelling of a single cysteine residue near the carboxylate binding site of lamb liver 6-phosphogluconate dehydrogenase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 8954568
Journal Arch Biochem Biophys
Year 1996
Volume 336
Pages 215-23
Authors Price NE, Cook PF
Title Kinetic and chemical mechanisms of the sheep liver 6-phosphogluconate dehydrogenase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 8766712
Journal FEBS Lett
Year 1996
Volume 389
Pages 263-7
Authors Hawes JW, Harper ET, Crabb DW, Harris RA
Title Structural and mechanistic similarities of 6-phosphogluconate and 3-hydroxyisobutyrate dehydrogenases reveal a new enzyme family, the 3-hydroxyacid dehydrogenases.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 8856059
Journal Eur J Biochem
Year 1996
Volume 240
Pages 592-9
Authors Hanau S, Rippa M, Bertelli M, Dallocchio F, Barrett MP
Title 6-Phosphogluconate dehydrogenase from Trypanosoma brucei. Kinetic analysis and inhibition by trypanocidal drugs.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9315293
Journal Biochem Mol Biol Int
Year 1997
Volume 43
Pages 153-60
Authors Giovannini PP, Rippa M, Dallocchio F, Tetaud M, Barrett MP, Hanau S
Title The cross-linking by o-phthalaldehyde of two amino acid residues at the active site of 6-phosphogluconate dehydrogenase.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9843373
Journal Biochemistry
Year 1998
Volume 37
Pages 15691-7
Authors Karsten WE, Chooback L, Cook PF
Title Glutamate 190 is a general acid catalyst in the 6-phosphogluconate-dehydrogenase-catalyzed reaction.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9920387
Journal Biochim Biophys Acta
Year 1998
Volume 1429
Pages 83-92
Authors Rippa M, Giovannini PP, Barrett MP, Dallocchio F, Hanau S
Title 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS)
Medline ID 98411456
PubMed ID 9737929
Journal J Mol Biol
Year 1998
Volume 282
Pages 667-81
Authors Phillips C, Dohnalek J, Gover S, Barrett MP, Adams MJ
Title A 2.8 A resolution structure of 6-phosphogluconate dehydrogenase from the protozoan parasite Trypanosoma brucei: comparison with the sheep enzyme accounts for differences in activity with coenzyme and substrate analogues.
Related PDB 1pgj
Related UniProtKB P31072
[24]
Resource
Comments
Medline ID
PubMed ID 10471272
Journal Biochemistry
Year 1999
Volume 38
Pages 11231-8
Authors Zhang L, Chooback L, Cook PF
Title Lysine 183 is the general base in the 6-phosphogluconate dehydrogenase-catalyzed reaction.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 9931298
Journal Biochem J
Year 1999
Volume 338
Pages 55-60
Authors Tetaud E, Hanau S, Wells JM, Le Page RW, Adams MJ, Arkison S, Barrett MP
Title 6-Phosphogluconate dehydrogenase from Lactococcus lactis: a role for arginine residues in binding substrate and coenzyme.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10848959
Journal Eur J Biochem
Year 2000
Volume 267
Pages 3442-52
Authors Moritz B, Striegel K, De Graaf AA, Sahm H
Title Kinetic properties of the glucose-6-phosphate and 6-phosphogluconate dehydrogenases from Corynebacterium glutamicum and their application for predicting pentose phosphate pathway flux in vivo.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 11430979
Journal Phytochemistry
Year 2001
Volume 57
Pages 1061-8
Authors Magel EA, Hillinger C, Wagner T, Holl W
Title Oxidative pentose phosphate pathway and pyridine nucleotides in relation to heartwood formation in Robinia pseudoacacia L.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11394739
Journal J Comput Aided Mol Des
Year 2001
Volume 15
Pages 465-75
Authors Bertelli M, El-Bastawissy E, Knaggs MH, Barrett MP, Hanau S, Gilbert IH
Title Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12818683
Journal Bioorg Med Chem
Year 2003
Volume 11
Pages 3205-14
Authors Dardonville C, Rinaldi E, Hanau S, Barrett MP, Brun R, Gilbert IH
Title Synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against African trypanosomiasis.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 12628648
Journal Bioorg Med Chem
Year 2003
Volume 11
Pages 1207-14
Authors Pasti C, Rinaldi E, Cervellati C, Dallocchio F, Hardre R, Salmon L, Hanau S
Title Sugar derivatives as new 6-phosphogluconate dehydrogenase inhibitors selective for the parasite Trypanosoma brucei.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 15189039
Journal J Med Chem
Year 2004
Volume 47
Pages 3427-37
Authors Dardonville C, Rinaldi E, Barrett MP, Brun R, Gilbert IH, Hanau S
Title Selective inhibition of Trypanosoma brucei 6-phosphogluconate dehydrogenase by high-energy intermediate and transition-state analogues.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 14698432
Journal Mol Biochem Parasitol
Year 2004
Volume 133
Pages 197-207
Authors Esteve MI, Cazzulo JJ
Title The 6-phosphogluconate dehydrogenase from Trypanosoma cruzi: the absence of two inter-subunit salt bridges as a reason for enzyme instability.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 15544466
Journal Curr Med Chem
Year 2004
Volume 11
Pages 2639-50
Authors Hanau S, Rinaldi E, Dallocchio F, Gilbert IH, Dardonville C, Adams MJ, Gover S, Barrett MP
Title 6-phosphogluconate dehydrogenase: a target for drugs in African trypanosomes.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of three domains (or regions). The CATH classifications of the C-terminal domain of the enzymes from sheep and Trypanosoma were different from each other, but their structures (2pgd & 1pgd, respectively) could be superimposed perfectly. So, these structures were clustered together in this entry.

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