3iar: Difference between revisions

Latest revision as of 07:42, 6 September 2023

The crystal structure of human adenosine deaminase

Structural highlights

3iar is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.52Å
Ligands:	3D1, GOL, NI, NO3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Function

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.^[11]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Hirschhorn R, Tzall S, Ellenbogen A. Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6171-5. PMID:2166947
↑ Adrian GS, Wiginton DA, Hutton JJ. Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. Mol Cell Biol. 1984 Sep;4(9):1712-7. PMID:6208479
↑ Bonthron DT, Markham AF, Ginsburg D, Orkin SH. Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency. J Clin Invest. 1985 Aug;76(2):894-7. PMID:3839802 doi:https://dx.doi.org/10.1172/JCI112050
↑ Akeson AL, Wiginton DA, Dusing MR, States JC, Hutton JJ. Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts. J Biol Chem. 1988 Nov 5;263(31):16291-6. PMID:3182793
↑ Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH. Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency. J Clin Invest. 1989 Feb;83(2):497-501. PMID:2783588 doi:https://dx.doi.org/10.1172/JCI113909
↑ Hirschhorn R. Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions. Hum Mutat. 1992;1(2):166-8. PMID:1284479 doi:https://dx.doi.org/10.1002/humu.1380010214
↑ Santisteban I, Arredondo-Vega FX, Kelly S, Mary A, Fischer A, Hummell DS, Lawton A, Sorensen RU, Stiehm ER, Uribe L, et al.. Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype. J Clin Invest. 1993 Nov;92(5):2291-302. PMID:8227344 doi:https://dx.doi.org/10.1172/JCI116833
↑ Yang DR, Huie ML, Hirschhorn R. Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). Clin Immunol Immunopathol. 1994 Feb;70(2):171-5. PMID:8299233
↑ Santisteban I, Arredondo-Vega FX, Kelly S, Debre M, Fischer A, Perignon JL, Hilman B, elDahr J, Dreyfus DH, Gelfand EW, et al.. Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site. Hum Mutat. 1995;5(3):243-50. PMID:7599635 doi:https://dx.doi.org/10.1002/humu.1380050309
↑ Arrendondo-Vega FX, Santisteban I, Notarangelo LD, El Dahr J, Buckley R, Roifman C, Conley ME, Hershfield MS. Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online. Hum Mutat. 1998;11(6):482. PMID:10200056 doi:<482::AID-HUMU15>3.0.CO;2-E 10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.0.CO;2-E
↑ Gines S, Marino M, Mallol J, Canela EI, Morimoto C, Callebaut C, Hovanessian A, Casado V, Lluis C, Franco R. Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. Biochem J. 2002 Jan 15;361(Pt 2):203-9. PMID:11772392

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OCA

[1] Hirschhorn R, Tzall S, Ellenbogen A. Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6171-5. PMID:2166947

[2] Adrian GS, Wiginton DA, Hutton JJ. Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. Mol Cell Biol. 1984 Sep;4(9):1712-7. PMID:6208479

[3] Bonthron DT, Markham AF, Ginsburg D, Orkin SH. Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency. J Clin Invest. 1985 Aug;76(2):894-7. PMID:3839802 doi:https://dx.doi.org/10.1172/JCI112050

[4] Akeson AL, Wiginton DA, Dusing MR, States JC, Hutton JJ. Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts. J Biol Chem. 1988 Nov 5;263(31):16291-6. PMID:3182793

[5] Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH. Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency. J Clin Invest. 1989 Feb;83(2):497-501. PMID:2783588 doi:https://dx.doi.org/10.1172/JCI113909

[6] Hirschhorn R. Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions. Hum Mutat. 1992;1(2):166-8. PMID:1284479 doi:https://dx.doi.org/10.1002/humu.1380010214

[7] Santisteban I, Arredondo-Vega FX, Kelly S, Mary A, Fischer A, Hummell DS, Lawton A, Sorensen RU, Stiehm ER, Uribe L, et al.. Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype. J Clin Invest. 1993 Nov;92(5):2291-302. PMID:8227344 doi:https://dx.doi.org/10.1172/JCI116833

[8] Yang DR, Huie ML, Hirschhorn R. Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). Clin Immunol Immunopathol. 1994 Feb;70(2):171-5. PMID:8299233

[9] Santisteban I, Arredondo-Vega FX, Kelly S, Debre M, Fischer A, Perignon JL, Hilman B, elDahr J, Dreyfus DH, Gelfand EW, et al.. Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site. Hum Mutat. 1995;5(3):243-50. PMID:7599635 doi:https://dx.doi.org/10.1002/humu.1380050309

[10] Arrendondo-Vega FX, Santisteban I, Notarangelo LD, El Dahr J, Buckley R, Roifman C, Conley ME, Hershfield MS. Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online. Hum Mutat. 1998;11(6):482. PMID:10200056 doi:<482::AID-HUMU15>3.0.CO;2-E 10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.0.CO;2-E

[11] Gines S, Marino M, Mallol J, Canela EI, Morimoto C, Callebaut C, Hovanessian A, Casado V, Lluis C, Franco R. Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. Biochem J. 2002 Jan 15;361(Pt 2):203-9. PMID:11772392

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[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

@@ Line 3: / Line 3: @@
 <StructureSection load='3iar' size='340' side='right'caption='[[3iar]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3iar]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IAR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3iar]] is a 1 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=3IAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IAR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3D1:(2R,3S,5R)-5-(6-AMINO-9H-PURIN-9-YL)-TETRAHYDRO-2-(HYDROXYMETHYL)FURAN-3-OL'>3D1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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]] 1.52&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1krm|1krm]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3D1:(2R,3S,5R)-5-(6-AMINO-9H-PURIN-9-YL)-TETRAHYDRO-2-(HYDROXYMETHYL)FURAN-3-OL'>3D1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3iar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iar OCA], [https://pdbe.org/3iar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iar RCSB], [https://www.ebi.ac.uk/pdbsum/3iar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iar 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>
+[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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 29: @@
 __TOC__
 </StructureSection>
-[[Category: Adenosine deaminase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Bray, J E]]
+[[Category: Bray JE]]
-[[Category: Burgess-Brown, N]]
+[[Category: Burgess-Brown N]]
-[[Category: Chaikuad, A]]
+[[Category: Chaikuad A]]
-[[Category: Delft, F von]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Hapka E]]
-[[Category: Hapka, E]]
+[[Category: Kavanagh KL]]
-[[Category: Kavanagh, K L]]
+[[Category: Muniz J]]
-[[Category: Muniz, J]]
+[[Category: Oppermann U]]
-[[Category: Oppermann, U]]
+[[Category: Ugochukwu E]]
-[[Category: Structural genomic]]
+[[Category: Weigelt J]]
-[[Category: Ugochukwu, E]]
+[[Category: Yue WW]]
-[[Category: Weigelt, J]]
+[[Category: Zhang Y]]
-[[Category: Yue, W W]]
+[[Category: Von Delft F]]
-[[Category: Zhang, Y]]
-[[Category: Adenosine]]
-[[Category: Deaminase]]
-[[Category: Disease mutation]]
-[[Category: Hereditary hemolytic anemia]]
-[[Category: Hydrolase]]
-[[Category: Nucleotide metabolism]]
-[[Category: Purine metabolism]]
-[[Category: Scid]]
-[[Category: Sgc]]

3iar: Difference between revisions

Latest revision as of 07:42, 6 September 2023

The crystal structure of human adenosine deaminase

Structural highlights

Disease

Function

Evolutionary Conservation

See Also

References

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