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| | ==Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 (ADA2)== | | ==Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 (ADA2)== |
| - | <StructureSection load='3lgd' size='340' side='right' caption='[[3lgd]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3lgd' size='340' side='right'caption='[[3lgd]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lgd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LGD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LGD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lgd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LGD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lgg|3lgg]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADA2, CECR1, CECR1/ADA2, IDGFL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3lgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lgd OCA], [https://pdbe.org/3lgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lgd RCSB], [https://www.ebi.ac.uk/pdbsum/3lgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lgd 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/Adenosine_deaminase Adenosine deaminase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lgd OCA], [http://pdbe.org/3lgd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lgd RCSB], [http://www.ebi.ac.uk/pdbsum/3lgd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lgd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/CECR1_HUMAN CECR1_HUMAN]] Cat-eye syndrome. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CECR1_HUMAN CECR1_HUMAN]] Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. Requires elevated adenosine levels for optimal enzyme activity. Binds to cell surfaces via proteoglycans and may play a role in the regulation of cell proliferation and differentiation, independently of its enzyme activity.<ref>PMID:20453107</ref> <ref>PMID:20147294</ref> | + | [https://www.uniprot.org/uniprot/ADA2_HUMAN ADA2_HUMAN] Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Required for the function of some acidic activation domains, which activate transcription from a distant site (By similarity). Binds double-stranded DNA. Binds dinucleosomes, probably at the linker region between neighboring nucleosomes. Plays a role in chromatin remodeling.<ref>PMID:19103755</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lg/3lgd_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lg/3lgd_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Adenosine deaminase|Adenosine deaminase]] | + | *[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosine deaminase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Zavialov, A V]] | + | [[Category: Zavialov AV]] |
| - | [[Category: Dimerization and receptor binding domain]]
| + | |
| - | [[Category: Glycoprotein]]
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| - | [[Category: Growth factor]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Secreted]]
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| - | [[Category: Tim barrel]]
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| Structural highlights
Function
ADA2_HUMAN Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Required for the function of some acidic activation domains, which activate transcription from a distant site (By similarity). Binds double-stranded DNA. Binds dinucleosomes, probably at the linker region between neighboring nucleosomes. Plays a role in chromatin remodeling.[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
Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp contrast with that of monomeric single domain ADA1. An extensive glycosylation and the presence of a conserved disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in contrast to ADA1, is specifically designed to act in the extracellular environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates large differences in the arrangement of the substrate-binding pockets. These structural differences explain the substrate and inhibitor specificity of adenosine deaminases and provide the basis for a rational design of ADA2-targeting drugs to modulate the immune system responses in pathophysiological conditions.
Structural basis for the growth factor activity of human adenosine deaminase ADA2.,Zavialov AV, Yu X, Spillmann D, Lauvau G, Zavialov AV J Biol Chem. 2010 Apr 16;285(16):12367-77. Epub 2010 Feb 9. PMID:20147294[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
- ↑ Zavialov AV, Yu X, Spillmann D, Lauvau G, Zavialov AV. Structural basis for the growth factor activity of human adenosine deaminase ADA2. J Biol Chem. 2010 Apr 16;285(16):12367-77. Epub 2010 Feb 9. PMID:20147294 doi:10.1074/jbc.M109.083527
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