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PDBsum entry 2v0n
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References listed in PDB file
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Key reference
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Title
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Structure of bef3- -Modified response regulator pled: implications for diguanylate cyclase activation, Catalysis, And feedback inhibition.
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Authors
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P.Wassmann,
C.Chan,
R.Paul,
A.Beck,
H.Heerklotz,
U.Jenal,
T.Schirmer.
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Ref.
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Structure, 2007,
15,
915-927.
[DOI no: ]
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PubMed id
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Abstract
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Cyclic di-guanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second
messenger involved in the regulation of cell surface-associated traits and
persistence. We have determined the crystal structure of PleD from Caulobacter
crescentus, a response regulator with a diguanylate cyclase (DGC) domain, in its
activated form. The BeF(3)(-) modification of its receiver domain causes
rearrangement with respect to an adaptor domain, which, in turn, promotes dimer
formation, allowing for the efficient encounter of two symmetric catalytic
domains. The substrate analog GTPalphaS and two putative cations are bound to
the active sites in a manner similar to adenylate cyclases, suggesting an
analogous two-metal catalytic mechanism. An allosteric c-di-GMP-binding mode
that crosslinks DGC and an adaptor domain had been identified before. Here, a
second mode is observed that crosslinks the DGC domains within a PleD dimer.
Both modes cause noncompetitive product inhibition by domain immobilization.
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Figure 5.
Figure 5. Substrate Analog GTPαS and Mg^2+ Bound to the
Active Site of PleD
The omit map for the ligands is
contoured at 3σ. The DGC domain is shown in ribbon
representation; the GGEEF signature hairpin is shown in dark
blue, and all interacting residues and the P loop main chain
(residues 328–331) are shown in full. (c-di-GMP)[2] bound to
the I[p] site of the DGC domain can be seen in the rear.
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Figure 6.
Figure 6. Crosslinking of the DGC Domains by c-di-GMP
(A) Ribbon diagram of the DGC dimer along its symmetry axis;
both (c-di-GMP)[2] ligands and interacting residues are shown in
full. The (c-di-GMP)[2] ligands are bound to the I site (I[P]
site and the I[s,DGC] site of the adjacent subunit).
(B)
Close-up view of the intercalated (c-di-GMP)[2] ligand, which
crosslinks the two DGC domains (dark- and light-green surface
representation) by binding to the I[p] (Arg359, Asp362, Arg390)
and the I[s,DGC] (R313′) site of the adjacent domain.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2007,
15,
915-927)
copyright 2007.
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