ORCID Profile
0000-0001-5683-1151
Current Organisation
Diamond Light Source Ltd
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Publisher: Springer Science and Business Media LLC
Date: 10-02-2017
DOI: 10.1038/SREP42166
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 (PA3825 EAL ) and PA1727 (MucR EAL ). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825 EAL 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.
Publisher: Elsevier BV
Date: 07-2004
Publisher: Proceedings of the National Academy of Sciences
Date: 24-07-2017
Abstract: A dedicated endoplasmic reticulum quality control (ERQC) machinery ensures the correct fold of secreted proteins bearing N-linked glycans, which constitute around a fifth of the whole proteome and are essential for many important cellular processes such as signaling, immunity, adhesion, transport, and metabolism. UDP-glucose:glycoprotein glucosyltransferase (UGGT) is the sole checkpoint enzyme of ERQC, flagging incorrectly folded glycoproteins for ER retention. Here, we describe crystal structures of full-length UGGT. We show that enzymatic activity depends on interdomain conformational mobility, indicating that the intrinsic flexibility of UGGT may endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Martin Austin Walsh.