5xsi

<StructureSection load='5xsi' size='340' side='right' caption='[[5xsi]], [[Resolution|resolution]] 2.20&Aring;' scene=''>

<table><tr><td colspan='2'>[[5xsi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XSI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XSI FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xsi OCA], [http://pdbe.org/5xsi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xsi RCSB], [http://www.ebi.ac.uk/pdbsum/5xsi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xsi ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

The Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterases (PDEs) that catalyze degradation of cyclic di-adenosine monophosphate (c-di-AMP) could be subdivided into two subfamilies based on the final product [5'-phosphadenylyl-adenosine (5'-pApA) or AMP]. In a previous study, we revealed that Rv2837c, a stand-alone DHH/DHHA1 PDE, employs a 5'-pApA internal flipping mechanism to produce AMPs. However, why the membrane-bound DHH/DHHA1 PDE can only degrade c-di-AMP to 5'-pApA remains obscure. Here, we report the crystal structure of the DHH/DHHA1 domain of GdpP (GdpP-C), and structures in complex with c-di-AMP, cyclic di-guanosine monophosphate (c-di-GMP), and 5'-pApA. Structural analysis reveals that GdpP-C binds nucleotide substrates quite differently from how Rv2837c does in terms of substrate-binding position. Accordingly, the nucleotide-binding site of the DHH/DHHA1 PDEs is organized into three (C, G, and R) subsites. For GdpP-C, in the C and G sites c-di-AMP binds and degrades into 5'-pApA, and its G site determines nucleotide specificity. To further degrade into AMPs, 5'-pApA must slide into the C and R sites for flipping and hydrolysis as in Rv2837c. Subsequent mutagenesis and enzymatic studies of GdpP-C and Rv2837c uncover the complete flipping process and reveal a unified catalytic mechanism for members of both DHH/DHHA1 PDE subfamilies.

 

== References ==

[[Category: Gu, L]]

[[Category: Wang, F]]

[[Category: Hydrolase]]

[[Category: Phosphodiesterase]]