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Crystal structure of an HD‐GYP domain cyclic‐di‐ GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre
Author(s) -
Bellini Dom,
Caly Delphine L.,
McCarthy Yvonne,
Bumann Mario,
An ShiQi,
Dow J. Maxwell,
Ryan Robert P.,
Walsh Martin A.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12447
Subject(s) - phosphodiesterase , second messenger system , enzyme , biology , biochemistry , stereochemistry , microbiology and biotechnology , chemistry , biophysics
Summary Bis‐(3′,5′) cyclic di‐guanylate (c‐di‐ GMP ) is a key bacterial second messenger that is implicated in the regulation of many crucial processes that include biofilm formation, motility and virulence. Cellular levels of c‐di‐ GMP are controlled through synthesis by GGDEF domain diguanylate cyclases and degradation by two classes of phosphodiesterase with EAL or HD‐GYP domains. Here, we have determined the structure of an enzymatically active HD‐GYP domain protein from P ersephonella marina ( Pm GH ) alone, in complex with substrate (c‐di‐ GMP ) and final reaction product ( GMP ). The structures reveal a novel trinuclear iron binding site, which is implicated in catalysis and identify residues involved in recognition of c‐di‐ GMP . This structure completes the picture of all domains involved in c‐di‐ GMP metabolism and reveals that the HD‐GYP family splits into two distinct subgroups containing bi‐ and trinuclear metal centres.