4u03: Difference between revisions
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The | ==Structure of the vibrio cholerae di-nucleotide cyclase (DncV) in complex with GTP and 5MTHFGLU2== | ||
<StructureSection load='4u03' size='340' side='right'caption='[[4u03]], [[Resolution|resolution]] 2.04Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4u03]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U03 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]] 2.041Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TLL:N-[4-({[(6S)-2-AMINO-5-METHYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GAMMA-GLUTAMYL-L-GLUTAMIC+ACID'>TLL</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=4u03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u03 OCA], [https://pdbe.org/4u03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u03 RCSB], [https://www.ebi.ac.uk/pdbsum/4u03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u03 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DNCV_VIBCH DNCV_VIBCH] Catalyzes the synthesis of cyclic AMP-GMP from ATP and GTP. Is also able to produce c-di-AMP and c-di-GMP from ATP and GTP, respectively; however, c-AMP-GMP is the dominant molecule produced by DncV in vivo. Is required for efficient V.cholerae intestinal colonization, and down-regulates the colonization-influencing process of chemotaxis. Is not active with dATP, TTP, UTP, and CTP. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cyclic dinucleotides are a newly expanded class of second messengers that contribute to the regulation of multiple different pathways in bacterial, eukaryotic, and archaeal cells. The recently identified Vibrio cholerae dinucleotide cyclase (DncV, the gene product of VC0179) can generate three different cyclic dinucleotides and preferentially synthesize a hybrid cyclic-GMP-AMP. Here, we report the crystal structural and functional studies of DncV. We unexpectedly observed a 5-methyltetrahydrofolate diglutamate (5MTHFGLU2) molecule bound in a surface pocket opposite the nucleotide substrate-binding groove of DncV. Subsequent mutagenesis and functional studies showed that the enzymatic activity of DncV is regulated by folate-like molecules, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis. Sequence analysis showed that the residues involved in 5MTHFGLU2 binding are highly conserved in DncV orthologs, implying the presence of this regulation mechanism in a wide variety of bacteria. | |||
Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates.,Zhu D, Wang L, Shang G, Liu X, Zhu J, Lu D, Wang L, Kan B, Zhang JR, Xiang Y Mol Cell. 2014 Sep 18;55(6):931-7. doi: 10.1016/j.molcel.2014.08.001. Epub 2014, Sep 4. PMID:25201413<ref>PMID:25201413</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4u03" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] | |||
[[Category: Xiang Y]] | |||
[[Category: Zhu DY]] | |||
Latest revision as of 18:18, 8 November 2023
Structure of the vibrio cholerae di-nucleotide cyclase (DncV) in complex with GTP and 5MTHFGLU2Structure of the vibrio cholerae di-nucleotide cyclase (DncV) in complex with GTP and 5MTHFGLU2
Structural highlights
FunctionDNCV_VIBCH Catalyzes the synthesis of cyclic AMP-GMP from ATP and GTP. Is also able to produce c-di-AMP and c-di-GMP from ATP and GTP, respectively; however, c-AMP-GMP is the dominant molecule produced by DncV in vivo. Is required for efficient V.cholerae intestinal colonization, and down-regulates the colonization-influencing process of chemotaxis. Is not active with dATP, TTP, UTP, and CTP. Publication Abstract from PubMedCyclic dinucleotides are a newly expanded class of second messengers that contribute to the regulation of multiple different pathways in bacterial, eukaryotic, and archaeal cells. The recently identified Vibrio cholerae dinucleotide cyclase (DncV, the gene product of VC0179) can generate three different cyclic dinucleotides and preferentially synthesize a hybrid cyclic-GMP-AMP. Here, we report the crystal structural and functional studies of DncV. We unexpectedly observed a 5-methyltetrahydrofolate diglutamate (5MTHFGLU2) molecule bound in a surface pocket opposite the nucleotide substrate-binding groove of DncV. Subsequent mutagenesis and functional studies showed that the enzymatic activity of DncV is regulated by folate-like molecules, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis. Sequence analysis showed that the residues involved in 5MTHFGLU2 binding are highly conserved in DncV orthologs, implying the presence of this regulation mechanism in a wide variety of bacteria. Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates.,Zhu D, Wang L, Shang G, Liu X, Zhu J, Lu D, Wang L, Kan B, Zhang JR, Xiang Y Mol Cell. 2014 Sep 18;55(6):931-7. doi: 10.1016/j.molcel.2014.08.001. Epub 2014, Sep 4. PMID:25201413[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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