DB code: D00450

CATH domain 3.40.50.1400 : Rossmann fold
3.40.50.1400 : Rossmann fold Catalytic domain
E.C. 4.99.1.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1400 : Rossmann fold S00842 D00828

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P32396 Ferrochelatase
EC 4.99.1.1
Heme synthase
Protoheme ferro-lyase
NP_388894.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF00762 (Ferrochelatase)
[Graphical View]

KEGG enzyme name
ferrochelatase
ferro-protoporphyrin chelatase
iron chelatase
heme synthetase
heme synthase
protoheme ferro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P32396 HEMH_BACSU Protoheme + 2 H(+) = protoporphyrin + Fe(2+). Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00860 Porphyrin and chlorophyll metabolism

Compound table
Substrates Products Intermediates
KEGG-id C02191 C00023 C00032 C00080
E.C.
Compound Protoporphyrin Fe2+ Protoheme H+
Type aromatic ring (with nitrogen atoms),carboxyl group heavy metal aromatic ring (with nitrogen atoms),carboxyl group,heavy metal others
ChEBI 15430
 15430
 		18248
 82664
 18248
 82664
 		17627
 26355
 17627
 26355
 		15378
 15378
PubChem 23925
 23925
 		1038
 1038
1ak1A01 Unbound Unbound Unbound
1c1hA01 Unbound Unbound Unbound
1c9eA01 Unbound Unbound Unbound
1dozA01 Unbound Unbound Unbound
1ld3A01 Unbound Unbound Unbound
1n0iA01 Unbound Unbound Unbound
1ak1A02 Unbound Unbound Unbound
1c1hA02 Analogue:MMP Unbound Unbound
1c9eA02 Unbound Unbound Analogue:MP1
1dozA02 Unbound Unbound Unbound
1ld3A02 Unbound Analogue:_ZN Unbound
1n0iA02 Unbound Analogue:_CD_910 Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P32396 & literature [6], [7], [9], [12] & [14]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ak1A01
1c1hA01
1c9eA01
1dozA01
1ld3A01
1n0iA01
1ak1A02 ASP 261;GLU 264 HIS 183(metal binding)
1c1hA02 ASP 261;GLU 264 HIS 183(metal binding)
1c9eA02 ASP 261;GLU 264 HIS 183(metal binding)
1dozA02 ASP 261;GLU 264 HIS 183(metal binding)
1ld3A02 ASP 261;GLU 264 HIS 183(metal binding)
1n0iA02 ASP 261;GLU 264 HIS 183(metal binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
[7]
p.1508
[9]
p.1915-1916
[10]
p.227-230
[12]
p.159
[14]
Fig.1

References
[1]
Resource
Comments
Medline ID
PubMed ID 6390167
Journal Mol Cell Biochem
Year 1984
Volume 64
Pages 127-37
Authors Cole SP, Marks GS
Title Ferrochelatase and N-alkylated porphyrins.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3895052
Journal Nat Prod Rep
Year 1985
Volume 2
Pages 19-47
Authors Leeper FJ
Title The biosynthesis of porphyrins, chlorophylls, and vitamin B12.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7947988
Journal Biochim Biophys Acta
Year 1994
Volume 1209
Pages 95-100
Authors Kohno H, Okuda M, Furukawa T, Tokunaga R, Taketani S
Title Site-directed mutagenesis of human ferrochelatase: identification of histidine-263 as a binding site for metal ions.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8119288
Journal Eur J Biochem
Year 1994
Volume 220
Pages 201-8
Authors Hansson M, Hederstedt L
Title Purification and characterisation of a water-soluble ferrochelatase from Bacillus subtilis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8749860
Journal Proteins
Year 1995
Volume 23
Pages 607-9
Authors Hansson M, Al-Karadaghi S
Title Purification, crystallization, and preliminary X-ray analysis of Bacillus subtilis ferrochelatase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8662602
Journal J Biol Chem
Year 1996
Volume 271
Pages 11810-6
Authors Gora M, Grzybowska E, Rytka J, Labbe-Bois R
Title Probing the active-site residues in Saccharomyces cerevisiae ferrochelatase by directed mutagenesis. In vivo and in vitro analyses.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 98046098
PubMed ID 9384565
Journal Structure
Year 1997
Volume 5
Pages 1501-10
Authors Al-Karadaghi S, Hansson M, Nikonov S, Jonsson B, Hederstedt L
Title Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis.
Related PDB 1ak1
Related UniProtKB P32396
[8]
Resource
Comments
Medline ID
PubMed ID 10582332
Journal Int J Biochem Cell Biol
Year 1999
Volume 31
Pages 995-1000
Authors Ferreira GC
Title Ferrochelatase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11215517
Journal Cell Mol Life Sci
Year 2000
Volume 57
Pages 1909-26
Authors Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP, Wang BC
Title Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 20171596
PubMed ID 10704318
Journal J Mol Biol
Year 2000
Volume 297
Pages 221-32
Authors Lecerof D, Fodje M, Hansson A, Hansson M, Al-Karadaghi S
Title Structural and mechanistic basis of porphyrin metallation by ferrochelatase.
Related PDB 1c1h 1c9e 1doz
Related UniProtKB P32396
[11]
Resource
Comments
Medline ID
PubMed ID 11336654
Journal Biochem J
Year 2001
Volume 356
Pages 217-22
Authors Franco R, Pereira AS, Tavares P, Mangravita A, Barber MJ, Moura I, Ferreira GC
Title Substitution of murine ferrochelatase glutamate-287 with glutamine or alanine leads to porphyrin substrate-bound variants.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11175906
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 156-60
Authors Wu CK, Dailey HA, Rose JP, Burden A, Sellers VM, Wang BC
Title The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis.
Related PDB 1hrk
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12196143
Journal Biochem Soc Trans
Year 2002
Volume 30
Pages 590-5
Authors Dailey HA
Title Terminal steps of haem biosynthesis.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12427010
Journal Biochemistry
Year 2002
Volume 41
Pages 13499-506
Authors Karlberg T, Lecerof D, Gora M, Silvegren G, Labbe-Bois R, Hansson M, Al-Karadaghi S
Title Metal binding to Saccharomyces cerevisiae ferrochelatase.
Related PDB 1l8x
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 14981080
Journal J Biol Chem
Year 2004
Volume 279
Pages 19977-86
Authors Shi Z, Ferreira GC
Title Probing the active site loop motif of murine ferrochelatase by random mutagenesis.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12761666
Journal J Biol Inorg Chem
Year 2003
Volume 8
Pages 452-8
Authors Lecerof D, Fodje MN, Alvarez Leon R, Olsson U, Hansson A, Sigfridsson E, Ryde U, Hansson M, Al-Karadaghi S
Title Metal binding to Bacillus subtilis ferrochelatase and interaction between metal sites.
Related PDB 1ld3 1n0i
Related UniProtKB

Comments
The reaction catalyzed by this enzyme is distinct from the other ones, such as elimination, catalyzed by other lyase enzymes.

Created Updated
2004-07-13 2009-02-26