7rtg: Difference between revisions

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-'''Unreleased structure'''
-The entry 7rtg is ON HOLD
+==Crystal Structure of the Human Adenosine Deaminase 1==
+<StructureSection load='7rtg' size='340' side='right'caption='[[7rtg]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7rtg]] 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=7RTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RTG 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]] 2.591&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7rtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rtg OCA], [https://pdbe.org/7rtg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rtg RCSB], [https://www.ebi.ac.uk/pdbsum/7rtg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rtg ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ADA_HUMAN ADA_HUMAN] Defects in ADA are the cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:[https://omim.org/entry/102700 102700]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA-SCID is an autosomal recessive form accounting for about 50% of non-X-linked SCIDs. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.<ref>PMID:2166947</ref> <ref>PMID:6208479</ref> <ref>PMID:3839802</ref> <ref>PMID:3182793</ref> <ref>PMID:2783588</ref> <ref>PMID:1284479</ref> <ref>PMID:8227344</ref> <ref>PMID:8299233</ref> <ref>PMID:7599635</ref> <ref>PMID:10200056</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ADA_HUMAN ADA_HUMAN] Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.<ref>PMID:11772392</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Homo sapiens adenosine deaminase 1 (HsADA1; UniProt P00813) is an immunologically relevant enzyme with roles in T-cell activation and modulation of adenosine metabolism and signaling. Patients with genetic deficiency in HsADA1 suffer from severe combined immunodeficiency, and HsADA1 is a therapeutic target in hairy cell leukemias. Historically, insights into the catalytic mechanism and the structural attributes of HsADA1 have been derived from studies of its homologs from Bos taurus (BtADA) and Mus musculus (MmADA). Here, the structure of holo HsADA1 is presented, as well as biochemical characterization that confirms its high activity and shows that it is active across a broad pH range. Structurally, holo HsADA1 adopts a closed conformation distinct from the open conformation of holo BtADA. Comparison of holo HsADA1 and MmADA reveals that MmADA also adopts a closed conformation. These findings challenge previous assumptions gleaned from BtADA regarding the conformation of HsADA1 that may be relevant to its immunological interactions, particularly its ability to bind adenosine receptors. From a broader perspective, the structural analysis of HsADA1 presents a cautionary tale for reliance on homologs to make structural inferences relevant to applications such as protein engineering or drug development.
-Authors:
+Catalytically active holo Homo sapiens adenosine deaminase I adopts a closed conformation.,Ma MT, Jennings MR, Blazeck J, Lieberman RL Acta Crystallogr D Struct Biol. 2022 Jan 1;78(Pt 1):91-103. doi:, 10.1107/S2059798321011785. Epub 2022 Jan 1. PMID:34981765<ref>PMID:34981765</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7rtg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Blazeck J]]
+[[Category: Jennings MR]]
+[[Category: Lieberman RL]]
+[[Category: Ma MT]]