DB code: T00101

RLCP classification	8.131.584400.264 : Isomerization
RLCP classification	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 29105	48066 48066	61553 61553
PubChem	32051 32051	65127 65127	439160 439160

1pmiA01	Bound:_ZN	Unbound	Unbound
1pmiA02	Unbound	Unbound	Unbound
1pmiA03	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	LYS 136;TYR 287;GLU 294	GLN 111;HIS 113;GLU 138;HIS 285(Zinc binding)
1pmiA02
1pmiA03

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.

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