DB code: S00366

RLCP classification 3.100.220195.81 : Transfer
CATH domain 3.40.50.1240 : Rossmann fold Catalytic domain
E.C. 5.4.2.1
CSA 1qhf
M-CSA 1qhf
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1240 : Rossmann fold S00365 S00363 D00460 D00514

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P62707 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase
BPG-dependent PGAM
PGAM
Phosphoglyceromutase
dPGM
EC 5.4.2.1
NP_415276.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489028.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00300 (His_Phos_1)
[Graphical View]
P0A5R6 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase
BPG-dependent PGAM
PGAM
Phosphoglyceromutase
dPGM
EC 5.4.2.1
NP_334917.1 (Protein)
NC_002755.2 (DNA/RNA sequence)
YP_006513819.1 (Protein)
NC_018143.1 (DNA/RNA sequence)
YP_177731.1 (Protein)
NC_000962.3 (DNA/RNA sequence)
PF00300 (His_Phos_1)
[Graphical View]
Q6MWZ7 (Possible phosphoglycerate mutase Gpm2
Phosphoglyceromutase
PGAM) (BPG-dependent PGAM)
YP_006516686.1 (Protein)
NC_018143.1 (DNA/RNA sequence)
YP_177944.1 (Protein)
NC_000962.3 (DNA/RNA sequence)
PF00300 (His_Phos_1)
[Graphical View]
P36623 Phosphoglycerate mutase
PGAM
EC 5.4.2.1
BPG-dependent PGAM
MPGM
Phosphoglyceromutase
NP_594889.1 (Protein)
NM_001020318.2 (DNA/RNA sequence)
PF00300 (His_Phos_1)
[Graphical View]
P00950 Phosphoglycerate mutase 1
PGAM 1
EC 5.4.2.1
BPG-dependent PGAM 1
MPGM 1
Phosphoglyceromutase 1
NP_012770.1 (Protein)
NM_001179718.1 (DNA/RNA sequence)
PF00300 (His_Phos_1)
[Graphical View]

KEGG enzyme name
phosphoglycerate mutase
phosphoglycerate phosphomutase
phosphoglyceromutase
glycerate phosphomutase (diphosphoglycerate cofactor)
monophosphoglycerate mutase
monophosphoglyceromutase
diphosphoglycomutase
diphosphoglycerate mutase
bisphosphoglyceromutase
GriP mutase
MPGM
PGA mutase
PGAM-i
PGAM
PGAM-d
PGM

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P62707 GPMA_ECOLI 2-phospho-D-glycerate = 3-phospho-D-glycerate. Homodimer.
P0A5R6 GPMA_MYCTU 2-phospho-D-glycerate = 3-phospho-D-glycerate.
Q6MWZ7 Q6MWZ7_MYCTU
P00950 PMG1_YEAST 2-phospho-D-glycerate = 3-phospho-D-glycerate. Homotetramer.
P36623 PMGY_SCHPO 2-phospho-D-glycerate = 3-phospho-D-glycerate. Monomer.

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C01159 C00631 C00197 C04262
E.C.
Compound 2,3-Bisphospho-D-glycerate 2-Phospho-D-glycerate 3-Phospho-D-glycerate Protein N(tau)-phospho-L-histidine
Type carboxyl group,phosphate group/phosphate ion carbohydrate,carboxyl group,phosphate group/phosphate ion carbohydrate,carboxyl group,phosphate group/phosphate ion
ChEBI 17720
17720
17835
17835
17794
17794
PubChem 186004
186004
439278
439278
439183
439183
1e58A Unbound Unbound Unbound Intermediate-bound:HIS_10-NEP
1e59A Analogue:VO3 Unbound Unbound Unbound
1riiA Unbound Analogue:GOL Unbound Unbound
1riiB Unbound Analogue:GOL Unbound Unbound
1riiC Unbound Unbound Unbound Unbound
1riiD Unbound Analogue:GOL Unbound Unbound
2a6pA Unbound Analogue:GOL-SO4 Unbound Unbound
2a6pB Unbound Analogue:GOL-SO4 Unbound Unbound
1bq3A Analogue:IHP Unbound Unbound Unbound
1bq3B Unbound Unbound Unbound Unbound
1bq3C Unbound Unbound Unbound Unbound
1bq3D Analogue:IHP Unbound Unbound Unbound
1bq4A Unbound Unbound Unbound Unbound
1bq4B Unbound Unbound Unbound Unbound
1bq4C Unbound Unbound Unbound Unbound
1bq4D Unbound Unbound Unbound Unbound
1qhfA Unbound Unbound Bound:3PG Unbound
1qhfB Unbound Unbound Bound:3PG Unbound
3pgmA Unbound Unbound Bound:3PG Unbound
4pgmA Unbound Unbound Unbound Unbound
4pgmB Unbound Unbound Unbound Unbound
4pgmC Unbound Unbound Unbound Unbound
4pgmD Unbound Unbound Unbound Unbound
5pgmA Unbound Unbound Unbound Unbound
5pgmB Unbound Unbound Unbound Unbound
5pgmC Unbound Unbound Unbound Unbound
5pgmD Unbound Unbound Unbound Unbound
5pgmE Unbound Unbound Unbound Unbound
5pgmF Unbound Unbound Unbound Unbound
5pgmG Unbound Unbound Unbound Unbound
5pgmH Unbound Unbound Unbound Unbound
1fztA Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00950, P62707, P36623 & literature [18]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1e58A HIS 10;GLU 88;ARG 9;ASN 16;ARG 61;HIS 183 HIS 10(Phosphorylation) Modified residue H10-NEP
1e59A HIS 10;GLU 88;ARG 9;ASN 16;ARG 61;HIS 183 HIS 10(Phosphorylation)
1riiA HIS 12;GLU 90;ARG 11;ASN 18;ARG 63;HIS 183 HIS 12(Phosphorylation)
1riiB HIS 12;GLU 90;ARG 11;ASN 18;ARG 63;HIS 183 HIS 12(Phosphorylation)
1riiC HIS 12;GLU 90;ARG 11;ASN 18;ARG 63;HIS 183 HIS 12(Phosphorylation)
1riiD HIS 12;GLU 90;ARG 11;ASN 18;ARG 63;HIS 183 HIS 12(Phosphorylation)
2a6pA HIS 13;GLU 85;ARG 12; ;ARG 64;HIS 147 HIS 13(Phosphorylation)
2a6pB HIS 13;GLU 85;ARG 12; ;ARG 64;HIS 147 HIS 13(Phosphorylation)
1bq3A HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq3B HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq3C HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq3D HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq4A HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq4B HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq4C HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1bq4D HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1qhfA HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1qhfB HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
3pgmA HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 179 HIS 8(Phosphorylation)
4pgmA HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
4pgmB HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
4pgmC HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
4pgmD HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmA HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmB HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmC HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmD HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmE HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmF HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmG HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
5pgmH HIS 8;GLU 86;ARG 7;ASN 14;ARG 59;HIS 181 HIS 8(Phosphorylation)
1fztA HIS 15;GLU 93;ARG 14;ASN 21;ARG 66;HIS 163 HIS 15(Phosphorylation)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Scheme II, p.741-742
[4]
Fig.3, p.125-128
[14]
p.455-457
[15]
p.1825-1826
[18]
Fig.5, p.1511-1515
[23]
p.1076-1077
[24]
p.1133-1137
[26]
p.82-83

References
[1]
Resource
Comments
Medline ID
PubMed ID 6251799
Journal Biochem Biophys Res Commun
Year 1980
Volume 95
Pages 132-9
Authors Hass LF, Miller KB
Title Human erythrocyte phosphoglycerate mutase: evidence for normal catalysis in the absence of added 2,3-bisphospho-D-glycerate.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6243955
Journal Biochemistry
Year 1980
Volume 19
Pages 738-43
Authors Blattler WA, Knowles JR
Title Phosphoglycerate mutases: stereochemical course of the phosphoryl group transfers catalyzed by the cofactor-dependent enzyme from rabbit muscle and the cofactor-independent enzyme from wheat germ.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 6115417
Journal Philos Trans R Soc Lond B Biol Sci
Year 1981
Volume 293
Pages 177-89
Authors Sternberg MJ, Cohen FE, Taylor WR, Feldmann RJ
Title Analysis and predication of structural motifs in the glycolytic enzymes.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID 81273329
PubMed ID 6115412
Journal Philos Trans R Soc Lond B Biol Sci
Year 1981
Volume 293
Pages 121-30
Authors Winn SI, Watson HC, Harkins RN, Fothergill LA
Title Structure and activity of phosphoglycerate mutase.
Related PDB 3pgm
Related UniProtKB P00950
[5]
Resource
Comments
Medline ID
PubMed ID 6282653
Journal Fed Proc
Year 1982
Volume 41
Pages 2424-31
Authors Knowles JR
Title Phospho transfer enzymes: lessons from stereochemistry.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 6318807
Journal Biochemistry
Year 1983
Volume 22
Pages 6130-4
Authors Hunt AG, Simplaceanu V, Hong JS, Ho C
Title Phosphorus-31 nuclear magnetic resonance investigation of membrane vesicles from Escherichia coli.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 6331428
Journal Biochem Biophys Res Commun
Year 1984
Volume 121
Pages 826-33
Authors Amato SV, Rose ZB, Liebman MN
Title Macro-structural organization of phosphoglycerate mutase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 6331429
Journal Biochem Biophys Res Commun
Year 1984
Volume 121
Pages 834-41
Authors Rose ZB, Kaklij GS
Title The effects of anions on phosphoglycerate mutase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1659318
Journal Arch Biochem Biophys
Year 1991
Volume 291
Pages 201-11
Authors Mendz GL
Title Stimulation of mutases and isomerases by vanadium.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8110200
Journal Biochem J
Year 1994
Volume 297
Pages 603-8
Authors Nairn J, Price NC, Fothergill-Gilmore LA, Walker GE, Fothergill JE, Dunbar B
Title The amino acid sequence of the small monomeric phosphoglycerate mutase from the fission yeast Schizosaccharomyces pombe.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8765231
Journal Biochim Biophys Acta
Year 1996
Volume 1296
Pages 69-75
Authors Nairn J, Price NC, Kelly SM, Rigden D, Fothergill-Gilmore LA, Krell T
Title Phosphoglycerate mutase from Schizosaccharomyces pombe: development of an expression system and characterisation of three histidine mutants of the enzyme.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9030753
Journal Eur J Biochem
Year 1997
Volume 243
Pages 306-14
Authors Seip S, Lanz R, Gutknecht R, Flukiger K, Erni B
Title The fructose transporter of Bacillus subtilis encoded by the lev operon: backbone assignment and secondary structure of the IIB(Lev) subunit.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9390410
Journal J Biomol NMR
Year 1997
Volume 10
Pages 309-10
Authors Uhrinova S, Uhrin D, Nairn J, Price NC, Fothergill-Gilmore LA, Barlow PN
Title Backbone assignment of double labelled 23.7 kDa phosphoglycerate mutase from Schizosaccharomyces pombe.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 98173871
PubMed ID 9512715
Journal J Mol Biol
Year 1998
Volume 276
Pages 449-59
Authors Rigden DJ, Alexeev D, Phillips SE, Fothergill-Gilmore LA
Title The 2.3 A X-ray crystal structure of S. cerevisiae phosphoglycerate mutase.
Related PDB 4pgm
Related UniProtKB P00950
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10531478
Journal Acta Crystallogr D Biol Crystallogr
Year 1999
Volume 55
Pages 1822-6
Authors Crowhurst GS, Dalby AR, Isupov MN, Campbell JW, Littlechild JA
Title Structure of a phosphoglycerate mutase:3-phosphoglyceric acid complex at 1.7 A.
Related PDB 1qhf
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10437801
Journal FEBS Lett
Year 1999
Volume 455
Pages 344-8
Authors Fraser HI, Kvaratskhelia M, White MF
Title The two analogous phosphoglycerate mutases of Escherichia coli.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10369755
Journal J Mol Biol
Year 1999
Volume 289
Pages 691-9
Authors Rigden DJ, Walter RA, Phillips SE, Fothergill-Gilmore LA
Title Polyanionic inhibitors of phosphoglycerate mutase: combined structural and biochemical analysis.
Related PDB 1bq3 1bq4
Related UniProtKB
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10064712
Journal J Mol Biol
Year 1999
Volume 286
Pages 1507-17
Authors Rigden DJ, Walter RA, Phillips SE, Fothergill-Gilmore LA
Title Sulphate ions observed in the 2.12 A structure of a new crystal form of S. cerevisiae phosphoglycerate mutase provide insights into understanding the catalytic mechanism.
Related PDB 5pgm
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11106417
Journal Eur J Biochem
Year 2000
Volume 267
Pages 7065-74
Authors Nairn J, Duncan D, Price NE, Kelly SM, Fothergill-Gilmore LA, Uhrinova S, Barlow PN, Rigden DJ, Price NC
Title Characterization of active-site mutants of Schizosaccharomyces pombe phosphoglycerate mutase. Elucidation of the roles of amino acids involved in substrate binding and catalysis.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11038361
Journal J Biol Chem
Year 2001
Volume 276
Pages 3247-53
Authors Bond CS, White MF, Hunter WN
Title High resolution structure of the phosphohistidine-activated form of Escherichia coli cofactor-dependent phosphoglycerate mutase.
Related PDB 1e58
Related UniProtKB P62707
[21]
Resource
Comments NMR, 21 STRUCTURES
Medline ID
PubMed ID 11237600
Journal J Mol Biol
Year 2001
Volume 306
Pages 275-90
Authors Uhrinova S, Uhrin D, Nairn J, Price NC, Fothergill-Gilmore LA, Barlow PN
Title Solution structure and dynamics of an open beta-sheet, glycolytic enzyme, monomeric 23.7 kDa phosphoglycerate mutase from Schizosaccharomyces pombe.
Related PDB 1fzt
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11514674
Journal Protein Sci
Year 2001
Volume 10
Pages 1835-46
Authors Rigden DJ, Bagyan I, Lamani E, Setlow P, Jedrzejas MJ
Title A cofactor-dependent phosphoglycerate mutase homolog from Bacillus stearothermophilus is actually a broad specificity phosphatase.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS).
Medline ID
PubMed ID 11884145
Journal J Mol Biol
Year 2002
Volume 316
Pages 1071-81
Authors Bond CS, White MF, Hunter WN
Title Mechanistic implications for Escherichia coli cofactor-dependent phosphoglycerate mutase based on the high-resolution crystal structure of a vanadate complex.
Related PDB 1e59
Related UniProtKB P62707
[24]
Resource
Comments
Medline ID
PubMed ID 11827481
Journal J Mol Biol
Year 2002
Volume 315
Pages 1129-43
Authors Rigden DJ, Mello LV, Setlow P, Jedrzejas MJ
Title Structure and mechanism of action of a cofactor-dependent phosphoglycerate mutase homolog from Bacillus stearothermophilus with broad specificity phosphatase activity.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11951058
Journal Med Sci Monit
Year 2002
Volume 8
Pages BR123-35
Authors Torshin IY
Title Functional maps of the junctions between interglobular contacts and active sites in glycolytic enzymes -- a comparative analysis of the biochemical and structural data.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12586342
Journal FEBS Lett
Year 2003
Volume 536
Pages 77-84
Authors Rigden DJ
Title Unexpected catalytic site variation in phosphoprotein phosphatase homologues of cofactor-dependent phosphoglycerate mutase.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 15258155
Journal J Biol Chem
Year 2004
Volume 279
Pages 39132-8
Authors Wang Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L, Gong W
Title Crystal structure of human bisphosphoglycerate mutase.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 15735341
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 309-15
Authors Muller P, Sawaya MR, Pashkov I, Chan S, Nguyen C, Wu Y, Perry LJ, Eisenberg D
Title The 1.70 angstroms X-ray crystal structure of Mycobacterium tuberculosis phosphoglycerate mutase.
Related PDB 1rii
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 16672613
Journal J Bacteriol
Year 2006
Volume 188
Pages 3589-99
Authors Watkins HA, Baker EN
Title Structural and functional analysis of Rv3214 from Mycobacterium tuberculosis, a protein with conflicting functional annotations, leads to its characterization as a phosphatase.
Related PDB 2a6p
Related UniProtKB

Comments
This enzyme is homologous to a phosphatase (E.C. 3.1.3.46; S00365 in EzCatDB).
This enzyme catalyzes a kind of intermolecular transfer reaction, which comprises the following steps of the reaction in the double-displacement mechanism.
(a) 2,3-BPG (cofactor) + enzyme => 3-PGA (or 2-PGA) (product) + phosphorylated enzyme
(b) 2-PGA (or 3-PGA) (substrate) + phosphorylated enzyme => 2,3-BPG (cofactor) + enzyme
Accoding to the literature [14], [18], [23], [24] & [26], the reaction mechanism of this enzyme seems to be as follows:
(a) 2,3-BPG (cofactor) + enzyme => 3-PGA (or 2-PGA) (product) + phosphorylated enzyme
(1) Arg59 and His181 modulate the nucleophilicity of His8, keeping His8 unprotonated.
(2) His8 makes a nucleophilic attack on one of the phosphoryl groups of 2,3-BPG, leading to a pentacovalent transition-state.
(3) The transition state seems to be stabilized by Arg7, Asn14, Arg59 and His181, whereas Glu86 acts as a general acid to protonate the leaving hydroxyl group, probably through a water molecule.
(b) 2-PGA (or 3-PGA) (substrate) + phosphorylated enzyme => 2,3-BPG (cofactor) + enzyme
(4) Glu86 now acts as a general base to deprotonate and activate another hydroxyl group of substrate.
(5) The activated acceptor, hydroxyl group, makes a nucleophilic attack on the phosphoryl group on His8, leading to a transition state.
(6) The transition state seems to be stabilized by Arg7, Asn14, Arg59 and His181.

Created Updated
2005-06-14 2015-10-27