PleD catalysis

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Overview

from Caulobacter crescentus is a response regulator with an unorthodox catalytic, diguanylate cyclase, output domain. It is composed of a canonical CheY-like response regulator receiver (, also called D1) domain, a Rec-like (, also called D2) adaptor domain, and a C-terminal domain that confers the catalytic acitvity.

The GGDEF domain is named after the highly conserved (in PleD it is GGEEF) that locates to a β-hairpin.

Substrate binding

The motif is part of the as identified in the structure of PleD in complex with . The GGDEF domain binds only one GTP substrate molecule. For the reaction to proceed, two GTP loaded GGDEF domains have to align antiparallely.

Complete active site

(The following model of the competent dimer is theoretical.)

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

After binding of the (here we show GMP, please update), it is believed that two GGDEF domains associate antiparallely to form a catalytically competent dimer (, ). Then, by inter-molecular nucleophilic in-line attack of the O3' atom onto the α-phosphorous of the other GTP substrate molecule, two phosphodiester bonds are formed under release of two pyrophosphate molecules (2 GTP -> c-di-GMP + 2 PPi).

References

Non-activated PleD structure 1w25:

• Chan C, Paul R, Samoray D, Amiot NC, Giese B, Jenal U, Schirmer T. Structural basis of activity and allosteric control of diguanylate cyclase. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17084-9. Epub 2004 Nov 29. PMID:15569936

Activated PleD structure 2v0n:

• Wassmann P, Chan C, Paul R, Beck A, Heerklotz H, Jenal U, Schirmer T. Structure of BeF3- -modified response regulator PleD: implications for diguanylate cyclase activation, catalysis, and feedback inhibition. Structure. 2007 Aug;15(8):915-27. PMID:17697997 doi:http://dx.doi.org/10.1016/j.str.2007.06.016