spacer
spacer

PDBsum entry 1c1h
Go to PDB code: 
protein ligands metals links
Lyase PDB id
1c1h

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
306 a.a. *
Ligands
MMP
Metals
_MG
Waters ×344
* Residue conservation analysis
PDB id:
1c1h
Name: Lyase
Title: Crystal structure of bacillus subtilis ferrochelatase in complex with n-methyl mesoporphyrin
Structure: Ferrochelatase. Chain: a. Synonym: heme synthetase. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.181     R-free:   0.231
Authors: D.Lecerof,M.Fodje,A.Hansson,M.Hansson,S.Al-Karadaghi
Key ref:
D.Lecerof et al. (2000). Structural and mechanistic basis of porphyrin metallation by ferrochelatase. J Mol Biol, 297, 221-232. PubMed id: 10704318 DOI: 10.1006/jmbi.2000.3569
Date:
22-Jul-99     Release date:   17-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P32396  (HEMH_BACSU) -  Coproporphyrin III ferrochelatase from Bacillus subtilis (strain 168)
Seq:
Struc: 		310 a.a.
306 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.99.1.9  - coproporphyrin ferrochelatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Fe-coproporphyrin III + 2 H+ = coproporphyrin III + Fe2+
Fe-coproporphyrin III
 + 2 × H(+)
 =
coproporphyrin III
Bound ligand (Het Group name = MMP)
matches with 85.71% similarity 		+ Fe(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Key reference    
 
 
DOI no: 10.1006/jmbi.2000.3569 J Mol Biol 297:221-232 (2000)
PubMed id: 10704318  
 
 
Structural and mechanistic basis of porphyrin metallation by ferrochelatase.
D.Lecerof, M.Fodje, A.Hansson, M.Hansson, S.Al-Karadaghi.
 
  ABSTRACT  
 
Ferrochelatase, the enzyme catalyzing metallation of protoporphyrin IX at the terminal step of heme biosynthesis, was co-crystallized with an isomer mixture of the potent inhibitor N-methylmesoporphyrin (N-MeMP). The X-ray structure revealed the active site of the enzyme, to which only one of the isomers was bound, and for the first time allowed characterization of the mode of porphyrin macrocycle distortion by ferrochelatase. Crystallization of ferrochelatase and N-MeMP in the presence of Cu(2+) leads to metallation and demethylation of N-MeMP. A mechanism of porphyrin distortion is proposed, which assumes that the enzyme holds pyrrole rings B, C and D in a vice-like grip and forces a 36 degrees tilt on ring A.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. (a) A stereo view of N-MeMP bound to ferrochelatase. The side-chains of amino acid residues in close contact with the inhibitor are also shown. WAT represents a solvent molecule coordinated to H183 and E264. This molecule may easily be replaced by a metal ion at the first stage of the enzymatic reaction. (b) A surface representation of the binding pocket for N-MeMP. The red and blue colors correspond to negative and positive surface potential, respectively. The position of the tilted pyrrole ring A shows that any changes in its conformation will result in steric clashes with protein side-chains. The Figure was produced with the program GRASP (Nicholls et al., 1991). 		Figure 7.
Figure 7. A stereo view of the structure of Cu:N-MeMP bound in the active site of ferrochelatase superimposed on a composite omit electron density map (blue). The density of the methyl group in this case is much weaker than the corresponding density in the N-MeMP complex (Figure 4). A difference (F[o] -F[c]) electron density for the Cu2+ contoured at 4s level is shown in red.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 297, 221-232) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21173279 C.V.Romão, D.Ladakis, S.A.Lobo, M.A.Carrondo, A.A.Brindley, E.Deery, P.M.Matias, R.W.Pickersgill, L.M.Saraiva, and M.J.Warren (2011).
Evolution in a family of chelatases facilitated by the introduction of active site asymmetry and protein oligomerization.
  Proc Natl Acad Sci U S A, 108, 97.
PDB codes: 2xvx 2xvz 2xwp 2xwq 2xws
21052751 M.D.Hansson, T.Karlberg, C.A.Söderberg, S.Rajan, M.J.Warren, S.Al-Karadaghi, S.E.Rigby, and M.Hansson (2011).
Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase.
  J Biol Inorg Chem, 16, 235-242.  
21222436 N.R.McIntyre, R.Franco, J.A.Shelnutt, and G.C.Ferreira (2011).
Nickel(II) chelatase variants directly evolved from murine ferrochelatase: porphyrin distortion and kinetic mechanism.
  Biochemistry, 50, 1535-1544.  
19543923 B.Szefczyk, M.N.Cordeiro, R.Franco, and J.A.Gomes (2009).
Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?
  J Biol Inorg Chem, 14, 1119-1128.  
19597542 B.Wu, J.Novelli, J.Foster, R.Vaisvila, L.Conway, J.Ingram, M.Ganatra, A.U.Rao, I.Hamza, and B.Slatko (2009).
The Heme Biosynthetic Pathway of the Obligate Wolbachia Endosymbiont of Brugia malayi as a Potential Anti-filarial Drug Target.
  PLoS Negl Trop Dis, 3, e475.  
19767646 R.E.Davidson, C.J.Chesters, and J.D.Reid (2009).
Metal ion selectivity and substrate inhibition in the metal ion chelation catalyzed by human ferrochelatase.
  J Biol Chem, 284, 33795-33799.  
18423489 T.Karlberg, M.D.Hansson, R.K.Yengo, R.Johansson, H.O.Thorvaldsen, G.C.Ferreira, M.Hansson, and S.Al-Karadaghi (2008).
Porphyrin binding and distortion and substrate specificity in the ferrochelatase reaction: the role of active site residues.
  J Mol Biol, 378, 1074-1083.
PDB codes: 2q2n 2q2o 2q3j
18273690 T.Masuda (2008).
Recent overview of the Mg branch of the tetrapyrrole biosynthesis leading to chlorophylls.
  Photosynth Res, 96, 121-143.  
17884090 A.E.Medlock, T.A.Dailey, T.A.Ross, H.A.Dailey, and W.N.Lanzilotta (2007).
A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase.
  J Mol Biol, 373, 1006-1016.
PDB codes: 2qd1 2qd2 2qd3 2qd4 2qd5
17261801 A.Medlock, L.Swartz, T.A.Dailey, H.A.Dailey, and W.N.Lanzilotta (2007).
Substrate interactions with human ferrochelatase.
  Proc Natl Acad Sci U S A, 104, 1789-1793.
PDB codes: 2hrc 2hre
17567154 H.A.Dailey, C.K.Wu, P.Horanyi, A.E.Medlock, W.Najahi-Missaoui, A.E.Burden, T.A.Dailey, and J.Rose (2007).
Altered orientation of active site residues in variants of human ferrochelatase. Evidence for a hydrogen bond network involved in catalysis.
  Biochemistry, 46, 7973-7979.
PDB codes: 2pnj 2po5 2po7
17566985 M.Hoggins, H.A.Dailey, C.N.Hunter, and J.D.Reid (2007).
Direct measurement of metal ion chelation in the active site of human ferrochelatase.
  Biochemistry, 46, 8121-8127.  
16835730 J.Yin, L.X.Xu, M.M.Cherney, E.Raux-Deery, A.A.Bindley, A.Savchenko, J.R.Walker, M.E.Cuff, M.J.Warren, and M.N.James (2006).
Crystal structure of the vitamin B12 biosynthetic cobaltochelatase, CbiXS, from Archaeoglobus fulgidus.
  J Struct Funct Genomics, 7, 37-50.
PDB code: 2dj5
16453119 M.D.Hansson, M.Lindstam, and M.Hansson (2006).
Crosstalk between metal ions in Bacillus subtilis ferrochelatase.
  J Biol Inorg Chem, 11, 325-333.  
16391725 M.O.Senge (2006).
Exercises in molecular gymnastics--bending, stretching and twisting porphyrins.
  Chem Commun (Camb), (), 243-256.  
17205631 P.Uehlinger, J.P.Ballini, H.van den Bergh, and G.Wagnières (2006).
On the role of iron and one of its chelating agents in the production of protoporphyrin IX generated by 5-aminolevulinic acid and its hexyl ester derivative tested on an epidermal equivalent of human skin.
  Photochem Photobiol, 82, 1069-1076.  
16469498 S.Al-Karadaghi, R.Franco, M.Hansson, J.A.Shelnutt, G.Isaya, and G.C.Ferreira (2006).
Chelatases: distort to select?
  Trends Biochem Sci, 31, 135-142.  
15884974 M.A.Verdecia, R.M.Larkin, J.L.Ferrer, R.Riek, J.Chory, and J.P.Noel (2005).
Structure of the Mg-chelatase cofactor GUN4 reveals a novel hand-shaped fold for porphyrin binding.
  PLoS Biol, 3, e151.
PDB code: 1y6i
15662683 Y.Shen, and U.Ryde (2005).
Reaction mechanism of porphyrin metallation studied by theoretical methods.
  Chemistry, 11, 1549-1564.  
15300829 S.J.Kwon, R.Petri, A.L.DeBoer, and C.Schmidt-Dannert (2004).
A high-throughput screen for porphyrin metal chelatases: application to the directed evolution of ferrochelatases for metalloporphyrin biosynthesis.
  Chembiochem, 5, 1069-1074.  
14981080 Z.Shi, and G.C.Ferreira (2004).
Probing the active site loop motif of murine ferrochelatase by random mutagenesis.
  J Biol Chem, 279, 19977-19986.  
12554938 K.Nilsson, D.Lecerof, E.Sigfridsson, and U.Ryde (2003).
An automatic method to generate force-field parameters for hetero-compounds.
  Acta Crystallogr D Biol Crystallogr, 59, 274-289.  
11939775 G.C.Ferreira, R.Franco, A.Mangravita, and G.N.George (2002).
Unraveling the substrate-metal binding site of ferrochelatase: an X-ray absorption spectroscopic study.
  Biochemistry, 41, 4809-4818.  
11980703 H.L.Schubert, E.Raux, A.A.Brindley, H.K.Leech, K.S.Wilson, C.P.Hill, and M.J.Warren (2002).
The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase.
  EMBO J, 21, 2068-2075.
PDB code: 1kyq
12207680 R.P.Sarkany (2002).
Erythropoietic protoporphyria (EPP) at 40. Where are we now?
  Photodermatol Photoimmunol Photomed, 18, 147-152.  
12081974 U.Olsson, A.Billberg, S.Sjövall, S.Al-Karadaghi, and M.Hansson (2002).
In vivo and in vitro studies of Bacillus subtilis ferrochelatase mutants suggest substrate channeling in the heme biosynthesis pathway.
  J Bacteriol, 184, 4018-4024.  
12116392 U.Ryde, L.Olsen, and K.Nilsson (2002).
Quantum chemical geometry optimizations in proteins using crystallographic raw data.
  J Comput Chem, 23, 1058-1070.  
12081474 Y.Lu, A.Sousa, R.Franco, A.Mangravita, G.C.Ferreira, I.Moura, and J.A.Shelnutt (2002).
Binding of protoporphyrin IX and metal derivatives to the active site of wild-type mouse ferrochelatase at low porphyrin-to-protein ratios.
  Biochemistry, 41, 8253-8262.  
  11598132 H.Atamna, J.Liu, and B.N.Ames (2001).
Heme deficiency selectively interrupts assembly of mitochondrial complex IV in human fibroblasts: revelance to aging.
  J Biol Chem, 276, 48410-48416.  
11599783 S.M.Kobus, S.G.Wong, and G.S.Marks (2001).
Isolation of regioisomers of N-alkylprotoporphyrin IX from chick embryo liver after treatment with porphyrinogenic xenobiotics.
  Can J Physiol Pharmacol, 79, 814-821.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

spacer
spacer