PDBsum entry 1gtk

Transferase

PDB id: 1gtk

Contents

Protein chain

294 a.a. *

Ligands

DPM

Waters ×320

* Residue conservation analysis

PDB id:

1gtk

Name:

Transferase

Title:

Time-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase

Structure:

Porphobilinogen deaminase. Chain: a. Fragment: three domains. Synonym: hydroxymethylbilane synthase, pbg, hmbs, hydroxymethylbilane synthase, pre-uroporphyrinogen synthase. Engineered: yes. Other_details: contains a dipyrromethane cofactor linked to cysteine 242

Source:

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

Biol. unit:

Monomer (from PDB file)

Resolution:

1.66Å R-factor: 0.200 R-free: 0.247

Authors:

J.R.Helliwell,Y.P.Nieh,J.Raftery,A.Cassetta,J.Habash,P.D.Carr, T.Ursby,M.Wulff,A.W.Thompson,A.C.Niemann,A.Haedener

Key ref:

J.R.Helliwell et al. (2003). Time-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase. Faraday Discuss, 122, 131. PubMed id: 12555854

Date:

16-Jan-02 Release date: 16-Jan-03

Protein chain

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

Seq: 313 a.a.

Struc: 294 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

Faraday Discuss 122:131 (2003)

PubMed id: 12555854

Time-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase.

J.R.Helliwell, Y.P.Nieh, J.Habash, P.F.Faulder, J.Raftery, M.Cianci, M.Wulff, A.Hädener.

ABSTRACT

The enzyme hydroxymethylbilane synthase (HMBS, EC 4.3.1.8), 313 amino acid residues and MW 34 kDa, also known as porphobilinogen deaminase (PBGD), catalyses the stepwise polymerization of four molecules of porphobilinogen (PBG) to the linear tetrapyrrole 1-hydroxymethylbilane. Several crystallographic structures of HMBS have been previously determined, most recently including by time-resolved Laue protein crystallography of the Lys59Gln mutant form with reaction initiation undertaken by use of a flow cell carrying the substrate PBG. In this paper we review these structures and add new molecular graphics representations and analyses. Moreover we present a new structure refined at 1.66 A resolution using diffraction data recorded at cryo-temperature (100 K) in an attempt at trapping the polypeptide loop (residues 47 to 58) in the vicinity of the enzyme active site, missing in all previous structure determinations. This loop still has not appeared in the electron density maps, in spite of the advantage of cryo-temperature, but nevertheless the 1.66 A cryo-structure extends the ensemble of known HMBS structures. The cryomodel of protein, cofactor and 320 bound water molecules has been refined to a final R-factor and R-free of 0.198 and 0.247 respectively; the PDB deposition codes, coordinates and structure factors are 1GTK and R1GTKSF respectively. Finally a protein comparison study is presented of the Mycobacterium tuberculosis (MTb) HMBS, with the E. coli HMBS. This has been done as preparation for future structural studies on the MTb HMBS from this important disease bearing organism. The overall amino acid sequence identity is 41%. Most interestingly there is a two-residue reduction in length of the loop referred to above (Asp 50 and Gly 58 being missing in the MTb form). This gives the hope that this loop will be less flexible and thus might become visible to crystallographic analysis.