PMID- 22120736
OWN - NLM
STAT- MEDLINE
DCOM- 20120405
LR  - 20131121
IS  - 1399-0047 (Electronic)
IS  - 0907-4449 (Linking)
VI  - 67
IP  - Pt 12
DP  - 2011 Dec
TI  - The structure and inhibition of a GGDEF diguanylate cyclase complexed with 
      (c-di-GMP)(2) at the active site.
PG  - 997-1008
LID - 10.1107/S090744491104039X [doi]
AB  - Cyclic diguanosine monophosphate (c-di-GMP) is a key signalling molecule involved 
      in regulating many important biological functions in bacteria. The synthesis of 
      c-di-GMP is catalyzed by the GGDEF-domain-containing diguanylate cyclase (DGC), 
      the activity of which is regulated by the binding of product at the allosteric 
      inhibitory (I) site. However, a significant number of GGDEF domains lack the RxxD 
      motif characteristic of the allosteric I site. Here, the structure of 
      XCC4471(GGDEF), the GGDEF domain of a DGC from Xanthomonas campestris, in complex 
      with c-di-GMP has been solved. Unexpectedly, the structure of the complex 
      revealed a GGDEF-domain dimer cross-linked by two molecules of c-di-GMP at the 
      strongly conserved active sites. In the complex (c-di-GMP)(2) adopts a novel 
      partially intercalated form, with the peripheral guanine bases bound to the 
      guanine-binding pockets and the two central bases stacked upon each other. 
      Alteration of the residues involved in specific binding to c-di-GMP led to 
      dramatically reduced K(d) values between XCC4471(GGDEF) and c-di-GMP. In 
      addition, these key residues are strongly conserved among the many thousands of 
      GGDEF-domain sequences identified to date. These results indicate a new 
      product-bound form for GGDEF-domain-containing proteins obtained via 
      (c-di-GMP)(2) binding at the active site. This novel XCC4471(GGDEF)-c-di-GMP 
      complex structure may serve as a general model for the design of lead compounds 
      to block the DGC activity of GGDEF-domain-containing proteins in X. campestris or 
      other microorganisms that contain multiple GGDEF-domain proteins.
FAU - Yang, Chao-Yu
AU  - Yang CY
AD  - Institute of Biochemistry, National Chung Hsing University, Taichung 40227, 
      Taiwan.
FAU - Chin, Ko-Hsin
AU  - Chin KH
FAU - Chuah, Mary Lay-Cheng
AU  - Chuah ML
FAU - Liang, Zhao-Xun
AU  - Liang ZX
FAU - Wang, Andrew H-J
AU  - Wang AH
FAU - Chou, Shan-Ho
AU  - Chou SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111118
PL  - United States
TA  - Acta Crystallogr D Biol Crystallogr
JT  - Acta crystallographica. Section D, Biological crystallography
JID - 9305878
RN  - 0 (Escherichia coli Proteins)
RN  - 61093-23-0 (bis(3',5')-cyclic diguanylic acid)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - EC 4.6.1.- (diguanylate cyclase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Cyclic GMP/*analogs & derivatives/chemistry/metabolism
MH  - Escherichia coli Proteins/*chemistry/metabolism
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phosphorus-Oxygen Lyases/*chemistry/metabolism
MH  - Protein Structure, Quaternary
MH  - Sequence Alignment
MH  - Structural Homology, Protein
MH  - Xanthomonas campestris/*enzymology
EDAT- 2011/11/29 06:00
MHDA- 2012/04/06 06:00
CRDT- 2011/11/29 06:00
PHST- 2011/07/26 00:00 [received]
PHST- 2011/09/30 00:00 [accepted]
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2012/04/06 06:00 [medline]
AID - S090744491104039X [pii]
AID - 10.1107/S090744491104039X [doi]
PST - ppublish
SO  - Acta Crystallogr D Biol Crystallogr. 2011 Dec;67(Pt 12):997-1008. doi: 
      10.1107/S090744491104039X. Epub 2011 Nov 18.