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Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases
Authors:
Dom
Bellini
(Diamond Light Source)
,
Sam
Horrell
(Diamond Light Source; University of Essex)
,
Andrew
Hutchin
(Diamond Light Source; University of Southampton)
,
Curtis
Phippen
(The University of Southampton)
,
Richard W.
Strange
(University of Essex)
,
Yuming
Cai
(The University of Southampton)
,
Armin
Wagner
(Diamond Light Source)
,
Jeremy S.
Webb
(The University of Southampton)
,
Ivo
Tews
(The University of Southampton)
,
Martin A.
Walsh
(Diamond Light Source)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Scientific Reports
, VOL 7
State:
Published (Approved)
Published:
February 2017
Diamond Proposal Number(s):
11175
,
8663
,
8889

Abstract: The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation.
Journal Keywords: Bacterial pathogenesis; X-ray crystallography
Diamond Keywords: Bacteria; Enzymes
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I02-Macromolecular Crystallography
,
I04-1-Macromolecular Crystallography (fixed wavelength)
Added On:
13/02/2017 11:58
Documents:
srep42166.pdf
Discipline Tags:
Pathogens
Infectious Diseases
Health & Wellbeing
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)