DB code: T00101

RLCP classification 8.131.584400.264 : Isomerization
8.113.904870.263 : Isomerization
CATH domain 2.60.120.10 : Jelly Rolls Catalytic domain
1.10.441.10 : Phosphomannose Isomerase; domain 2
2.60.120.10 : Jelly Rolls
E.C. 5.3.1.8
CSA 1pmi
M-CSA 1pmi
MACiE

CATH domain Related DB codes (homologues)
2.60.120.10 : Jelly Rolls S00145 S00155 D00842 D00843 T00255 M00216

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P34948 Mannose-6-phosphate isomerase
EC 5.3.1.8
Phosphohexomutase
Phosphomannose isomerase
PMI
XP_714562.1 (Protein)
XM_709469.1 (DNA/RNA sequence)
PF01238 (PMI_typeI)
[Graphical View]

KEGG enzyme name
mannose-6-phosphate isomerase
phosphomannose isomerase
phosphohexomutase
phosphohexoisomerase
mannose phosphate isomerase
phosphomannoisomerase
D-mannose-6-phosphate ketol-isomerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P34948 MPI_CANAL D-mannose 6-phosphate = D-fructose 6- phosphate. Monomer. Cytoplasm (Probable). Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00051 Fructose and mannose metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00275 C00085
E.C.
Compound Zinc D-Mannose 6-phosphate D-Fructose 6-phosphate
Type heavy metal carbohydrate,phosphate group/phosphate ion carbohydrate,phosphate group/phosphate ion
ChEBI 29105
48066
61553
PubChem 32051
65127
439160
1pmiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound
1pmiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1pmiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P34948 & literature [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1pmiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 136;TYR 287;GLU 294 GLN 111;HIS 113;GLU 138;HIS 285(Zinc binding)
1pmiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pmiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
FIGURE 7, p.5781-5782
[6]
p.477
[11]
FIGURE 8, p.2932

References
[1]
Resource
Comments
Medline ID
PubMed ID 1660728
Journal Biochimie
Year 1991
Volume 73
Pages 1241-4
Authors Willem R, Malaisse-Lagae F, Malaisse WJ
Title Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates: distinction of the 1-monodeutero-isotopomers of D-fructose 6-phosphate by 1H NMR spectroscopy.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1448058
Journal Mol Cell Biochem
Year 1992
Volume 115
Pages 137-42
Authors Malaisse-Lagae F, Willem R, Penders M, Malaisse WJ
Title Dual anomeric specificity of phosphomannoisomerase assessed by 2D phase sensitive 13C EXSY NMR.
Related PDB
Related UniProtKB
[3]
Resource
Comments CHEMICAL LABELLING OF CYS-149, AND PARTIAL PROTEIN SEQUENCE.
Medline ID
PubMed ID 8260497
Journal Biochemistry
Year 1993
Volume 32
Pages 14139-44
Authors Coulin F, Magnenat E, Proudfoot AE, Payton MA, Scully P, Wells TN
Title Identification of Cys-150 in the active site of phosphomannose isomerase from Candida albicans.
Related PDB
Related UniProtKB
[4]
Resource
Comments ACTIVE SITE ARG-303, AND SEQUENCE OF 299-311.
Medline ID 94235645
PubMed ID 8180205
Journal Biochemistry
Year 1994
Volume 33
Pages 5777-82
Authors Wells TN, Scully P, Magnenat E
Title Arginine 304 is an active site residue in phosphomannose isomerase from Candida albicans.
Related PDB
Related UniProtKB P34948
[5]
Resource
Comments
Medline ID
PubMed ID 8145246
Journal J Mol Biol
Year 1994
Volume 237
Pages 349-50
Authors Tolley S, Davies G, Hubbard RE, Smith DJ, Proudfoot AE, Payton MA, Cleasby A, Wonacott A, Wells TN
Title Crystallization and preliminary X-ray analysis of Candida albicans phosphomannose isomerase.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID 96196885
PubMed ID 8612079
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 470-9
Authors Cleasby A, Wonacott A, Skarzynski T, Hubbard RE, Davies GJ, Proudfoot AE, Bernard AR, Payton MA, Wells TN
Title The x-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 angstrom resolution.
Related PDB 1pmi
Related UniProtKB P34948
[7]
Resource
Comments
Medline ID
PubMed ID 9118997
Journal Eur J Biochem
Year 1997
Volume 244
Pages 325-33
Authors Smith JJ, Thomson AJ, Proudfoot AE, Wells TN
Title Identification of an Fe(III)-dihydroxyphenylalanine site in recombinant phosphomannose isomerase from Candida albicans.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9507048
Journal Biochim Biophys Acta
Year 1998
Volume 1382
Pages 5-7
Authors Jensen SO, Reeves PR
Title Domain organisation in phosphomannose isomerases (types I and II).
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11697049
Journal J Enzyme Inhib
Year 2001
Volume 16
Pages 287-92
Authors Salvati L, Mattu M, Tiberi F, Polticelli F, Ascenzi P
Title Inhibition of Saccharomyces cerevisiae phosphomannose isomerase by the NO-donor S-nitroso-acetyl-penicillamine.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12042299
Journal J Biol Chem
Year 2002
Volume 277
Pages 26351-5
Authors Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM, Ratcliffe PJ, Pugh CW, Schofield CJ
Title Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 15005628
Journal Biochemistry
Year 2004
Volume 43
Pages 2926-34
Authors Roux C, Lee JH, Jeffery CJ, Salmon L
Title Inhibition of type I and type II phosphomannose isomerases by the reaction intermediate analogue 5-phospho-D-arabinonohydroxamic acid supports a catalytic role for the metal cofactor.
Related PDB
Related UniProtKB

Comments
Comparing the active site of this enzyme with its homologous enzyme (PDB, 1qwr), conserved Glu294 and Lys136 may act as catalytic residues, and Gln111 may be displaced by substrate binding.
The catalytic cofactor, zinc ion, is bound to two oxygen atoms of substrate, O1 & O2. This enzyme catalyzes two successive isomerization (shift of double-bond position) (see [4], [6] & [11]).
(A) Isomerization (shift of double-bond position; from O=C-C to O-C=C):
(A1) A general base abstract a proton from C2 atom (single-bonded atom). Considering the active-site, Glu294 may acts as the base. This reaction leads to the formation of ene-diol intermediate, forming a double-bond between C1 and C2 atoms. Tyr287 may modulate the function of Glu294 through a hydrogen bond.
(A2) Lys136 may facilitate proton transfer from O2 atom to O1 atom as base-acid, along with zinc ion.
(B) Isomerization (shift of double-bond position; from C=C-O to C-C=O):
(B1) A general acid protonates to C1 atom (double-bonded atom) (from Si face). Considering the active-site, Glu294 may acts as the acid. Tyr287 may modulate the function of Glu294 through a hydrogen bond.

Created Updated
2005-05-27 2009-02-26