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| | ==Crystal structure of full length Rv0805 in complex with 5'-AMP== | | ==Crystal structure of full length Rv0805 in complex with 5'-AMP== |
| - | <StructureSection load='3ib8' size='340' side='right' caption='[[3ib8]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3ib8' size='340' side='right'caption='[[3ib8]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ib8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IB8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IB8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ib8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IB8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hy1|2hy1]], [[2hyp|2hyp]], [[2hyo|2hyo]], [[3ib7|3ib7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv0805 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3ib8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ib8 OCA], [https://pdbe.org/3ib8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ib8 RCSB], [https://www.ebi.ac.uk/pdbsum/3ib8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ib8 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span></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=3ib8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ib8 OCA], [http://pdbe.org/3ib8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ib8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ib8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ib8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CPDA_MYCTO CPDA_MYCTO]] Hydrolyzes cAMP to 5'-AMP. Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes. May play a role in pathogenicity, not only by hydrolyzing cAMP, but also by altering properties of the cell wall (By similarity).[HAMAP-Rule:MF_00905] | + | [https://www.uniprot.org/uniprot/CNPD3_MYCTU CNPD3_MYCTU] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP (PubMed:16313172, PubMed:18757371). Can use 2',3'-cAMP, 2',3'-cGMP, 3',5'-cAMP, 3',5'-cGMP and 3',5'-cUMP (PubMed:16313172, PubMed:18757371, PubMed:19801656). Hydrolysis of 2',3'-cAMP produces a mixture of 3'-AMP (major product) and 2'-AMP (minor product) (PubMed:18757371). In vitro, is 150-fold more active in hydrolyzing 2',3'-cAMP than 3',5'-cAMP (PubMed:18757371). Can also hydrolyze the model substrates p-nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP)) and p-nitrophenyl phenylphosphonate (pNPPP) (PubMed:16313172, PubMed:18757371, PubMed:19801656). Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes (PubMed:16313172). May play a role in pathogenicity, not only by hydrolyzing cAMP, but also by altering properties of the cell wall (PubMed:19801656).<ref>PMID:16313172</ref> <ref>PMID:18757371</ref> <ref>PMID:19801656</ref> Overexpression elicits a transcriptional response that is independent of the phosphodiesterase activity. It does not alter the levels of cAMP-CRP regulated genes, even though cAMP levels are reduced in cells.<ref>PMID:23835087</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ib/3ib8_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ib/3ib8_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[Phosphodiesterase|Phosphodiesterase]] | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dermol, U]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Podobnik, M]] | + | [[Category: Dermol U]] |
| - | [[Category: Alpha-beta fold]] | + | [[Category: Podobnik M]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallophosphoesterase]]
| + | |
| - | [[Category: Swapped-dimer]]
| + | |
| Structural highlights
3ib8 is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.8Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CNPD3_MYCTU Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP (PubMed:16313172, PubMed:18757371). Can use 2',3'-cAMP, 2',3'-cGMP, 3',5'-cAMP, 3',5'-cGMP and 3',5'-cUMP (PubMed:16313172, PubMed:18757371, PubMed:19801656). Hydrolysis of 2',3'-cAMP produces a mixture of 3'-AMP (major product) and 2'-AMP (minor product) (PubMed:18757371). In vitro, is 150-fold more active in hydrolyzing 2',3'-cAMP than 3',5'-cAMP (PubMed:18757371). Can also hydrolyze the model substrates p-nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP)) and p-nitrophenyl phenylphosphonate (pNPPP) (PubMed:16313172, PubMed:18757371, PubMed:19801656). Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes (PubMed:16313172). May play a role in pathogenicity, not only by hydrolyzing cAMP, but also by altering properties of the cell wall (PubMed:19801656).[1] [2] [3] Overexpression elicits a transcriptional response that is independent of the phosphodiesterase activity. It does not alter the levels of cAMP-CRP regulated genes, even though cAMP levels are reduced in cells.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mycobacterium tuberculosis utilizes many mechanisms to establish itself within the macrophage, and bacterially derived cAMP is important in modulating the host cellular response. Although the genome of M. tuberculosis is endowed with a number of mammalian-like adenylyl cyclases, only a single cAMP phosphodiesterase has been identified that can decrease levels of cAMP produced by the bacterium. We present the crystal structure of the full-length and sole cAMP phosphodiesterase, Rv0805, found in M. tuberculosis, whose orthologs are present only in the genomes of slow growing and pathogenic mycobacteria. The dimeric core catalytic domain of Rv0805 adopts a metallophosphoesterase-fold, and the C-terminal region builds the active site and contributes to multiple substrate utilization. Localization of Rv0805 to the cell wall is dependent on its C terminus, and expression of either wild type or mutationally inactivated Rv0805 in M. smegmatis alters cell permeability to hydrophobic cytotoxic compounds. Rv0805 may therefore play a key role in the pathogenicity of mycobacteria, not only by hydrolyzing bacterial cAMP, but also by moonlighting as a protein that can alter cell wall functioning.
A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability.,Podobnik M, Tyagi R, Matange N, Dermol U, Gupta AK, Mattoo R, Seshadri K, Visweswariah SS J Biol Chem. 2009 Nov 20;284(47):32846-57. Epub 2009 Sep 29. PMID:19801656[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shenoy AR, Sreenath N, Podobnik M, Kovacevic M, Visweswariah SS. The Rv0805 gene from Mycobacterium tuberculosis encodes a 3',5'-cyclic nucleotide phosphodiesterase: biochemical and mutational analysis. Biochemistry. 2005 Dec 6;44(48):15695-704. PMID:16313172 doi:10.1021/bi0512391
- ↑ Keppetipola N, Shuman S. A phosphate-binding histidine of binuclear metallophosphodiesterase enzymes is a determinant of 2',3'-cyclic nucleotide phosphodiesterase activity. J Biol Chem. 2008 Nov 7;283(45):30942-9. PMID:18757371 doi:10.1074/jbc.M805064200
- ↑ Podobnik M, Tyagi R, Matange N, Dermol U, Gupta AK, Mattoo R, Seshadri K, Visweswariah SS. A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability. J Biol Chem. 2009 Nov 20;284(47):32846-57. Epub 2009 Sep 29. PMID:19801656 doi:10.1074/jbc.M109.049635
- ↑ Matange N, Hunt DM, Buxton RS, Visweswariah SS. Overexpression of the Rv0805 phosphodiesterase elicits a cAMP-independent transcriptional response. Tuberculosis (Edinb). 2013 Sep;93(5):492-500. PMID:23835087 doi:10.1016/j.tube.2013.05.004
- ↑ Podobnik M, Tyagi R, Matange N, Dermol U, Gupta AK, Mattoo R, Seshadri K, Visweswariah SS. A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability. J Biol Chem. 2009 Nov 20;284(47):32846-57. Epub 2009 Sep 29. PMID:19801656 doi:10.1074/jbc.M109.049635
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