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| | <StructureSection load='2pgf' size='340' side='right'caption='[[2pgf]], [[Resolution|resolution]] 1.89Å' scene=''> | | <StructureSection load='2pgf' size='340' side='right'caption='[[2pgf]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pgf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemamoeba_vivax Haemamoeba vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PGF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pgf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PGF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.89Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qvn|2qvn]], [[2pgr|2pgr]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pv111245 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 Haemamoeba vivax])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] </span></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=2pgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgf OCA], [https://pdbe.org/2pgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pgf RCSB], [https://www.ebi.ac.uk/pdbsum/2pgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pgf ProSAT]</span></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=2pgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgf OCA], [https://pdbe.org/2pgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pgf RCSB], [https://www.ebi.ac.uk/pdbsum/2pgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pgf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ADA_PLAVS ADA_PLAVS] Catalyzes the hydrolytic deamination of adenosine to produce inosine (PubMed:19728741). Unlike mammalian adenosine deaminases, also catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI) (PubMed:19728741). Plays an essential role in the purine salvage pathway which allows the parasite to use host cell purines for the synthesis of nucleic acids (PubMed:19728741).<ref>PMID:19728741</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosine deaminase]] | |
| - | [[Category: Haemamoeba vivax]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Larson, E T]] | + | [[Category: Plasmodium vivax]] |
| - | [[Category: Merritt, E A]] | + | [[Category: Larson ET]] |
| - | [[Category: Structural genomic]] | + | [[Category: Merritt EA]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallo-dependent hydrolase]]
| + | |
| - | [[Category: Msgpp]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Sgpp]]
| + | |
| Structural highlights
Function
ADA_PLAVS Catalyzes the hydrolytic deamination of adenosine to produce inosine (PubMed:19728741). Unlike mammalian adenosine deaminases, also catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI) (PubMed:19728741). Plays an essential role in the purine salvage pathway which allows the parasite to use host cell purines for the synthesis of nucleic acids (PubMed:19728741).[1]
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
Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore, interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial ADA accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5'-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax ADA in complex with adenosine, guanosine, and the picomolar inhibitor 2'-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes.
Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity.,Larson ET, Deng W, Krumm BE, Napuli A, Mueller N, Van Voorhis WC, Buckner FS, Fan E, Lauricella A, DeTitta G, Luft J, Zucker F, Hol WG, Verlinde CL, Merritt EA J Mol Biol. 2008 Sep 12;381(4):975-88. Epub 2008 Jun 24. PMID:18602399[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ho MC, Cassera MB, Madrid DC, Ting LM, Tyler PC, Kim K, Almo SC, Schramm VL. Structural and metabolic specificity of methylthiocoformycin for malarial adenosine deaminases. Biochemistry. 2009 Oct 13;48(40):9618-26. PMID:19728741 doi:http://dx.doi.org/10.1021/bi9012484
- ↑ Larson ET, Deng W, Krumm BE, Napuli A, Mueller N, Van Voorhis WC, Buckner FS, Fan E, Lauricella A, DeTitta G, Luft J, Zucker F, Hol WG, Verlinde CL, Merritt EA. Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity. J Mol Biol. 2008 Sep 12;381(4):975-88. Epub 2008 Jun 24. PMID:18602399 doi:http://dx.doi.org/10.1016/j.jmb.2008.06.048
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