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Structural studies of domain movement in active-site mutants of porphobilinogen deaminase from Bacillus megaterium.

Guo, J; Erskine, P; Coker, AR; Wood, SP; Cooper, JB; (2017) Structural studies of domain movement in active-site mutants of porphobilinogen deaminase from Bacillus megaterium. Acta Crystallogr F Struct Biol Commun , 73 (11) pp. 612-620. 10.1107/S2053230X17015436. Green open access

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Abstract

The enzyme porphobilinogen deaminase (PBGD) is one of the key enzymes in tetrapyrrole biosynthesis. It catalyses the formation of a linear tetrapyrrole from four molecules of the substrate porphobilinogen (PBG). It has a dipyrromethane cofactor (DPM) in the active site which is covalently linked to a conserved cysteine residue through a thioether bridge. The substrate molecules are linked to the cofactor in a stepwise head-to-tail manner during the reaction, which is catalysed by a conserved aspartate residue: Asp82 in the B. megaterium enzyme. Three mutations have been made affecting Asp82 (D82A, D82E and D82N) and their crystal structures have been determined at resolutions of 2.7, 1.8 and 1.9 Å, respectively. These structures reveal that whilst the D82E mutant possesses the DPM cofactor, in the D82N and D82A mutants the cofactor is likely to be missing, incompletely assembled or disordered. Comparison of the mutant PBGD structures with that of the wild-type enzyme shows that there are significant domain movements and suggests that the enzyme adopts `open' and `closed' conformations, potentially in response to substrate binding.

Type: Article
Title: Structural studies of domain movement in active-site mutants of porphobilinogen deaminase from Bacillus megaterium.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1107/S2053230X17015436
Publisher version: https://doi.org/10.1107/S2053230X17015436
Language: English
Additional information: © International Union of Crystallography. This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Bacillus megaterium, porphobilinogen deaminase, protein crystallography, structural biology, tetrapyrrole biosynthesis
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/10037527
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