PDBsum entry 1eb3

Dehydratase

PDB id: 1eb3

Contents

Protein chain

340 a.a. *

Ligands

DSB

Metals

_ZN

Waters ×402

* Residue conservation analysis

PDB id:

1eb3

Name:

Dehydratase

Title:

Yeast 5-aminolaevulinic acid dehydratase 4,7-dioxosebacic acid complex

Structure:

5-aminolaevulinic acid dehydratase. Chain: a. Synonym: alad, porphobilinogen synthase. Engineered: yes. Other_details: complex with 4,7-dioxosebacic acid

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: ns1(jm109/pns1). Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Octamer (from PDB file)

Resolution:

1.75Å R-factor: 0.239 R-free: 0.308

Authors:

P.T.Erskine,L.Coates,R.Newbold,A.A.Brindley,F.Stauffer,S.P.Wood, M.J.Warren,J.B.Cooper,P.M.Shoolingin-Jordan,R.Neier

Key ref:

P.T.Erskine et al. (2001). The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors. FEBS Lett, 503, 196-200. PubMed id: 11513881 DOI: 10.1016/S0014-5793(01)02721-1

Date:

18-Jul-01 Release date: 02-Aug-01

Protein chain

P05373  (HEM2_YEAST) -  Delta-aminolevulinic acid dehydratase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 342 a.a.

Struc: 340 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.24 - porphobilinogen synthase.
• Pathway: Porphyrin Biosynthesis (early stages)
• Reaction: 2 5-aminolevulinate = porphobilinogen + 2 H2O + H⁺

2 × 5-aminolevulinate (Bound ligand (Het Group name = DSB) matches with 43.75% similarity) = porphobilinogen + 2 × H2O + H(+)

• Cofactor: Zn(2+)

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

Added reference

DOI no: 10.1016/S0014-5793(01)02721-1

FEBS Lett 503:196-200 (2001)

PubMed id: 11513881

The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors.

P.T.Erskine, L.Coates, R.Newbold, A.A.Brindley, F.Stauffer, S.P.Wood, M.J.Warren, J.B.Cooper, P.M.Shoolingin-Jordan, R.Neier.

ABSTRACT

The structures of 5-aminolaevulinic acid dehydratase complexed with two irreversible inhibitors (4-oxosebacic acid and 4,7-dioxosebacic acid) have been solved at high resolution. Both inhibitors bind by forming a Schiff base link with Lys 263 at the active site. Previous inhibitor binding studies have defined the interactions made by only one of the two substrate moieties (P-side substrate) which bind to the enzyme during catalysis. The structures reported here provide an improved definition of the interactions made by both of the substrate molecules (A- and P-side substrates). The most intriguing result is the novel finding that 4,7-dioxosebacic acid forms a second Schiff base with the enzyme involving Lys 210. It has been known for many years that P-side substrate forms a Schiff base (with Lys 263) but until now there has been no evidence that binding of A-side substrate involves formation of a Schiff base with the enzyme. A catalytic mechanism involving substrate linked to the enzyme through Schiff bases at both the A- and P-sites is proposed.

Selected figure(s)

Figure 1.
Fig. 1. The reaction catalysed by 5-aminolaevulinic acid dehydratase (ALAD). Two molecules of 5-aminolaevulinic acid are condensed to form the pyrrole porphobilinogen.

Figure 3.
Fig. 3. The refined electron density maps (shown in purple) for the inhibitors 4,7-dioxosebacic acid at 1.75 Å resolution (top) and 4-oxosebacic acid at 1.8 Å resolution (bottom). The maps are contoured at 1.5 rms (top) and 1.2 rms (bottom).

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2001, 503, 196-200) copyright 2001.

Figures were selected by an automated process.