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| | ==Crystal Structure of Human Deoxyguanosine Kinase== | | ==Crystal Structure of Human Deoxyguanosine Kinase== |
| - | <StructureSection load='2ocp' size='340' side='right' caption='[[2ocp]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='2ocp' size='340' side='right'caption='[[2ocp]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ocp]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1jag 1jag]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OCP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ocp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1jag 1jag]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OCP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jag|1jag]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jag|1jag]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DGUOK, DGK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DGUOK, DGK ([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'>[http://en.wikipedia.org/wiki/Deoxyguanosine_kinase Deoxyguanosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.113 2.7.1.113] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Deoxyguanosine_kinase Deoxyguanosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.113 2.7.1.113] </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=2ocp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ocp OCA], [http://pdbe.org/2ocp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ocp RCSB], [http://www.ebi.ac.uk/pdbsum/2ocp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ocp 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=2ocp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ocp OCA], [https://pdbe.org/2ocp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ocp RCSB], [https://www.ebi.ac.uk/pdbsum/2ocp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ocp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DGUOK_HUMAN DGUOK_HUMAN]] Defects in DGUOK are the cause of mitochondrial DNA depletion syndrome type 3 (MTDPS3) [MIM:[http://omim.org/entry/251880 251880]]. A disorder characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.<ref>PMID:12205643</ref> <ref>PMID:15639197</ref> | + | [[https://www.uniprot.org/uniprot/DGUOK_HUMAN DGUOK_HUMAN]] Defects in DGUOK are the cause of mitochondrial DNA depletion syndrome type 3 (MTDPS3) [MIM:[https://omim.org/entry/251880 251880]]. A disorder characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.<ref>PMID:12205643</ref> <ref>PMID:15639197</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DGUOK_HUMAN DGUOK_HUMAN]] Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:8706825</ref> | + | [[https://www.uniprot.org/uniprot/DGUOK_HUMAN DGUOK_HUMAN]] Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents.<ref>PMID:8706825</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Deoxyguanosine kinase]] | | [[Category: Deoxyguanosine kinase]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Eklund, H]] | | [[Category: Eklund, H]] |
| | [[Category: Eriksson, S]] | | [[Category: Eriksson, S]] |
| Structural highlights
Disease
[DGUOK_HUMAN] Defects in DGUOK are the cause of mitochondrial DNA depletion syndrome type 3 (MTDPS3) [MIM:251880]. A disorder characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.[1] [2]
Function
[DGUOK_HUMAN] Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents.[3]
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
Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.
Structural basis for substrate specificities of cellular deoxyribonucleoside kinases.,Johansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B, Eriksson S, Eklund H Nat Struct Biol. 2001 Jul;8(7):616-20. PMID:11427893[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Salviati L, Sacconi S, Mancuso M, Otaegui D, Camano P, Marina A, Rabinowitz S, Shiffman R, Thompson K, Wilson CM, Feigenbaum A, Naini AB, Hirano M, Bonilla E, DiMauro S, Vu TH. Mitochondrial DNA depletion and dGK gene mutations. Ann Neurol. 2002 Sep;52(3):311-7. PMID:12205643 doi:10.1002/ana.10284
- ↑ Wang L, Limongelli A, Vila MR, Carrara F, Zeviani M, Eriksson S. Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes. Mol Genet Metab. 2005 Jan;84(1):75-82. PMID:15639197 doi:10.1016/j.ymgme.2004.09.005
- ↑ Wang L, Hellman U, Eriksson S. Cloning and expression of human mitochondrial deoxyguanosine kinase cDNA. FEBS Lett. 1996 Jul 15;390(1):39-43. PMID:8706825
- ↑ Johansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B, Eriksson S, Eklund H. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Nat Struct Biol. 2001 Jul;8(7):616-20. PMID:11427893 doi:10.1038/89661
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