View source for 5yrp


==Crystal structure of the EAL domain of Mycobacterium smegmatis DcpA==
<StructureSection load='5yrp' size='340' side='right'caption='[[5yrp]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yrp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YRP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.99&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yrp OCA], [https://pdbe.org/5yrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yrp RCSB], [https://www.ebi.ac.uk/pdbsum/5yrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yrp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0QUG3_MYCS2 A0QUG3_MYCS2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian cGMP-regulated phosphodiesterases, Anabaenaadenylyl cyclases and Escherichia coli transcription activator FhlA) domain containing bifunctional enzyme DcpA (diguanylate cyclase and phosphodiesterase A) that catalyzes the synthesis and hydrolysis of c-di-GMP. Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments.

The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.,Chen HJ, Li N, Luo Y, Jiang YL, Zhou CZ, Chen Y, Li Q Biochem J. 2018 Apr 9;475(7):1295-1308. doi: 10.1042/BCJ20180079. PMID:29555845<ref>PMID:29555845</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5yrp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Chen HJ]]
[[Category: Chen Y]]
[[Category: Jiang YL]]
[[Category: Li Q]]
[[Category: Luo Y]]
[[Category: Zhou CZ]]
[[Category: Li N]]