PDBsum entry 1ah5

Transferase

PDB id: 1ah5

Contents

Protein chain

299 a.a. *

Ligands

DPM

Waters ×177

* Residue conservation analysis

PDB id:

1ah5

Name:

Transferase

Title:

Reduced form selenomethionine-labelled hydroxymethylbilane synthase determined by mad

Structure:

Hydroxymethylbilane synthase. Chain: a. Fragment: three domains. Synonym: porphobilinogen deaminase. Engineered: yes. Other_details: contains a dipyrromethane cofactor linked to the residue cysteine 242

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Monomer (from PDB file)

Resolution:

2.40Å R-factor: 0.168 R-free: 0.235

Authors:

J.R.Helliwell,Y.P.Nieh,S.J.Harrop,A.Cassetta

Key ref:

A.Hädener et al. (1999). Determination of the structure of seleno-methionine-labelled hydroxymethylbilane synthase in its active form by multi-wavelength anomalous dispersion. Acta Crystallogr D Biol Crystallogr, 55, 631-643. PubMed id: 10089459 DOI: 10.1107/S0907444998014711

Date:

13-Apr-97 Release date: 15-Oct-97

Protein chain

P06983  (HEM3_ECOLI) -  Porphobilinogen deaminase from Escherichia coli (strain K12)

Seq: 313 a.a.

Struc: 299 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.61 - hydroxymethylbilane synthase.
• Pathway: Porphyrin Biosynthesis (early stages)
• Reaction: 4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH4⁺

4 × porphobilinogen + H2O = hydroxymethylbilane (Bound ligand (Het Group name = DPM) matches with 49.18% similarity) + 4 × NH4(+)

• Cofactor: Dipyrromethane

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1107/S0907444998014711

Acta Crystallogr D Biol Crystallogr 55:631-643 (1999)

PubMed id: 10089459

Determination of the structure of seleno-methionine-labelled hydroxymethylbilane synthase in its active form by multi-wavelength anomalous dispersion.

A.Hädener, P.K.Matzinger, A.R.Battersby, S.McSweeney, A.W.Thompson, A.P.Hammersley, S.J.Harrop, A.Cassetta, A.Deacon, W.N.Hunter, Y.P.Nieh, J.Raftery, N.Hunter, J.R.Helliwell.

ABSTRACT

The enzyme hydroxymethylbilane synthase (HMBS, E.C. 4.3.1.8) catalyzes the conversion of porphobilinogen into hydroxymethylbilane, a key intermediate for the biosynthesis of heme, chlorophylls, vitamin B12 and related macrocycles. The enzyme is found in all organisms, except viruses. The crystal structure of the selenomethionine-labelled enzyme ([SeMet]HMBS) from Escherichia coli has been solved by the multi-wavelength anomalous dispersion (MAD) experimental method using the Daresbury SRS station 9.5. In addition, [SeMet]HMBS has been studied by MAD at the Grenoble ESRF MAD beamline BM14 (BL19) and this work is described especially with respect to the use of the ESRF CCD detector. The structure at ambient temperature has been refined, the R factor being 16.8% at 2. 4 A resolution. The dipyrromethane cofactor of the enzyme is preserved in its reduced form in the crystal and its geometrical shape is in full agreement with the crystal structures of authentic dipyrromethanes. Proximal to the reactive C atom of the reduced cofactor, spherical density is seen consistent with there being a water molecule ideally placed to take part in the final step of the enzyme reaction cycle. Intriguingly, the loop with residues 47-58 is not ordered in the structure of this form of the enzyme, which carries no substrate. Direct experimental study of the active enzyme is now feasible using time-resolved Laue diffraction and freeze-trapping, building on the structural work described here as the foundation.

Selected figure(s)

Figure 2.
Figure 2 Oxidation states of the cofactor of the HMBS holoenzyme (R represents the apoenzyme moiety). (a) Dipyrromethane structure (catalytically active); for labelling conventions, see text; (b) dipyrromethene structure (inactive); (c) dipyrromethenone structure (inactive). A = CH[2]COO^-; P = CH[2]CH[2]COO^-.

Figure 6.
Figure 6 Geometry of the reduced dipyrromethane cofactor. For values of bond distances and bond angles, see Table 6-. (a) Dipyrromethane core structure and thioether moiety used to search the CSD; (b) atom names and bond types, and (c) angle types used for the parameterization of the cofactor and the Cys residue to which it is attached.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 631-643) copyright 1999.

Figures were selected by an automated process.