PDBsum entry 3d8s

Lyase

PDB id

3d8s

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Contents

			Protein chain

					250 a.a. *

			Ligands

					GOL

			Waters ×115

* Residue conservation analysis

PDB id:

3d8s

Links

Name:

Lyase

Title:

Thermus thermophilus uroporphyrinogen iii synthase

Structure:

Uroporphyrinogen-iii synthase. Chain: a. Engineered: yes

Source:

Thermus thermophilus. Organism_taxid: 262724. Strain: hb27. Gene: tt_c0312. Expressed in: escherichia coli.

Resolution:

2.00Å

R-factor:

0.207

R-free:

0.259

Authors:

H.L.Schubert

Key ref:

H.L.Schubert et al. (2008). Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex. Biochemistry, 47, 8648-8655. PubMed id: 18651750

Date:

23-May-08

Release date:

05-Aug-08

PROCHECK

	Headers

	References

Protein chain

Q72KM1 (Q72KM1_THET2) - Uroporphyrinogen-III synthase from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27)

Seq: Struc:					253 a.a. 250 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.4.2.1.75 - uroporphyrinogen-III synthase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Porphyrin Biosynthesis (early stages)

Reaction:

hydroxymethylbilane = uroporphyrinogen III + H2O

hydroxymethylbilane	=	uroporphyrinogen III	+	H2O

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

Added reference

	Biochemistry 47:8648-8655 (2008)
PubMed id: 18651750

Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex.
H.L.Schubert, J.D.Phillips, A.Heroux, C.P.Hill.

ABSTRACT

Uroporphyrinogen III synthase (U3S) catalyzes the asymmetrical cyclization of a linear tetrapyrrole to form the physiologically relevant uroporphyrinogen III (uro'gen III) isomer during heme biosynthesis. Here, we report four apoenzyme and one product complex crystal structures of the Thermus thermophilus (HB27) U3S protein. The overlay of eight crystallographically unique U3S molecules reveals a huge range of conformational flexibility, including a "closed" product complex. The product, uro'gen III, binds between the two domains and is held in place by a network of hydrogen bonds between the product's side chain carboxylates and the protein's main chain amides. Interactions of the product A and B ring carboxylate side chains with both structural domains of U3S appear to dictate the relative orientation of the domains in the closed enzyme conformation and likely remain intact during catalysis. The product C and D rings are less constrained in the structure, consistent with the conformational changes required for the catalytic cyclization with inversion of D ring orientation. A conserved tyrosine residue is potentially positioned to facilitate loss of a hydroxyl from the substrate to initiate the catalytic reaction.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20506125

G.Layer, J.Reichelt, D.Jahn, and D.W.Heinz (2010).
Structure and function of enzymes in heme biosynthesis.

Protein Sci, 19, 1137-1161.

20485863

S.Clavero, D.F.Bishop, U.Giger, M.E.Haskins, and R.J.Desnick (2010).
Feline congenital erythropoietic porphyria: two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation.

Mol Med, 16, 381-388.

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.