Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site
- 1 September 1992
- journal article
- Published by Springer Nature in Nature
- Vol. 359 (6390) , 33-39
- https://doi.org/10.1038/359033a0
Abstract
The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.Keywords
This publication has 33 references indexed in Scilit:
- Cloning and characterization of the hemA region of the Bacillus subtilis chromosomeJournal of Bacteriology, 1990
- Isolation and characterisation of a cDNA clone for a chlorophyll synthesis enzyme from Euglena gracilisEuropean Journal of Biochemistry, 1989
- The Mouse Porphobilinogen Deaminase GeneJournal of Biological Chemistry, 1989
- Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminaseBiochemistry, 1988
- Rat porphobilinogen deaminase cDNA: nucleotide sequence of the erythropoletic formNucleic Acids Research, 1988
- Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminaseFEBS Letters, 1987
- Biosynthesis of the natural porphyrins: proof that hydroxymethylbilane synthase (porphobilinogen deaminase) uses a novel binding group in its catalytic actionJournal of the Chemical Society, Chemical Communications, 1987
- Nucleotide sequence of thehemClocus encoding porpbobilinogen deaminase ofEscherichia coliK12Nucleic Acids Research, 1986
- Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminaseNucleic Acids Research, 1986
- Mechanism and stereochemistry of the porphobilinogen deaminase and protoporphyrinogen IX oxidase reactions: stereospecific manipulation of hydrogen atoms at the four methylene bridges during the biosynthesis of haem.Journal of the Chemical Society, Perkin Transactions 1, 1984