|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==crystal structure of human galactokinase complexed with MgAMPPNP and galactose== | | ==crystal structure of human galactokinase complexed with MgAMPPNP and galactose== |
| - | <StructureSection load='1wuu' size='340' side='right' caption='[[1wuu]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='1wuu' size='340' side='right'caption='[[1wuu]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1wuu]] is a 4 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=1WUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WUU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1wuu]] is a 4 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=1WUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WUU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.5Å</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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GALK1 ([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=1wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wuu OCA], [https://pdbe.org/1wuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wuu RCSB], [https://www.ebi.ac.uk/pdbsum/1wuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wuu 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/Galactokinase Galactokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.6 2.7.1.6] </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=1wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wuu OCA], [http://pdbe.org/1wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wuu RCSB], [http://www.ebi.ac.uk/pdbsum/1wuu PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN]] Defects in GALK1 are the cause of galactosemia II (GALCT2) [MIM:[http://omim.org/entry/230200 230200]]. Galactosemia II is an autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses.<ref>PMID:10521295</ref> <ref>PMID:10790206</ref> <ref>PMID:11231902</ref> <ref>PMID:11139256</ref> <ref>PMID:12694189</ref> <ref>PMID:15024738</ref> | + | [https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Defects in GALK1 are the cause of galactosemia II (GALCT2) [MIM:[https://omim.org/entry/230200 230200]. Galactosemia II is an autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses.<ref>PMID:10521295</ref> <ref>PMID:10790206</ref> <ref>PMID:11231902</ref> <ref>PMID:11139256</ref> <ref>PMID:12694189</ref> <ref>PMID:15024738</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN]] Major enzyme for galactose metabolism. | + | [https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Major enzyme for galactose metabolism. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/1wuu_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/1wuu_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> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wuu ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| Line 32: |
Line 31: |
| | </div> | | </div> |
| | <div class="pdbe-citations 1wuu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1wuu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Galactokinase|Galactokinase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Galactokinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Holden, H M]] | + | [[Category: Holden HM]] |
| - | [[Category: Reece, R J]] | + | [[Category: Reece RJ]] |
| - | [[Category: Thoden, J B]] | + | [[Category: Thoden JB]] |
| - | [[Category: Timson, D J]] | + | [[Category: Timson DJ]] |
| - | [[Category: Galactosemia]]
| + | |
| - | [[Category: Ghmp superfamily]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
GALK1_HUMAN Defects in GALK1 are the cause of galactosemia II (GALCT2) [MIM:230200. Galactosemia II is an autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses.[1] [2] [3] [4] [5] [6]
Function
GALK1_HUMAN Major enzyme for galactose metabolism.
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
Galactokinase functions in the Leloir pathway for galactose metabolism by catalyzing the MgATP-dependent phosphorylation of the C-1 hydroxyl group of alpha-D-galactose. The enzyme is known to belong to the GHMP superfamily of small molecule kinases and has attracted significant research attention for well over 40 years. Approximately 20 mutations have now been identified in human galactokinase, which result in the diseased state referred to as Type II galactosemia. Here we report the three-dimensional architecture of human galactokinase with bound alpha-D-galactose and Mg-AMPPNP. The overall fold of the molecule can be described in terms of two domains with the active site wedged between them. The N-terminal domain is dominated by a six-stranded mixed beta-sheet whereas the C-terminal motif contains six alpha-helices and two layers of anti-parallel beta-sheet. Those residues specifically involved in sugar binding include Arg37, Glu43, His44, Asp46, Gly183, Asp186, and Tyr236. The C-1 hydroxyl group of alpha-D-galactose sits within 3.3 A of the gamma-phosphorus of the nucleotide and 3.4 A of the guanidinium group of Arg37. The carboxylate side chain of Asp186 lies within approximately 3.2 A of the C-2 hydroxyl group of alpha-D-galactose and the guanidinium group of Arg37. Both Arg37 and Asp186 are strictly conserved among both prokaryotic and eukaryotic galactokinases. In addition to providing molecular insight into the active site geometry of the enzyme, the model also provides a structural framework upon which to more fully understand the consequences of the those mutations known to give rise to Type II galactosemia.
Molecular structure of human galactokinase: implications for type II galactosemia.,Thoden JB, Timson DJ, Reece RJ, Holden HM J Biol Chem. 2005 Mar 11;280(10):9662-70. Epub 2004 Dec 7. PMID:15590630[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kalaydjieva L, Perez-Lezaun A, Angelicheva D, Onengut S, Dye D, Bosshard NU, Jordanova A, Savov A, Yanakiev P, Kremensky I, Radeva B, Hallmayer J, Markov A, Nedkova V, Tournev I, Aneva L, Gitzelmann R. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet. 1999 Nov;65(5):1299-307. PMID:10521295 doi:S0002-9297(07)62136-3
- ↑ Kolosha V, Anoia E, de Cespedes C, Gitzelmann R, Shih L, Casco T, Saborio M, Trejos R, Buist N, Tedesco T, Skach W, Mitelmann O, Ledee D, Huang K, Stambolian D. Novel mutations in 13 probands with galactokinase deficiency. Hum Mutat. 2000;15(5):447-53. PMID:10790206 doi:<447::AID-HUMU6>3.0.CO;2-M 10.1002/(SICI)1098-1004(200005)15:5<447::AID-HUMU6>3.0.CO;2-M
- ↑ Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K, Hsiao KJ, Choeh K, Yang Y, Cao Q, Reichardt JK, Niihira S, Imamura T, Yamano T. A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, "Osaka," in Asians. Am J Hum Genet. 2001 Apr;68(4):1036-42. Epub 2001 Feb 23. PMID:11231902 doi:S0002-9297(07)61428-1
- ↑ Hunter M, Angelicheva D, Levy HL, Pueschel SM, Kalaydjieva L. Novel mutations in the GALK1 gene in patients with galactokinase deficiency. Hum Mutat. 2001;17(1):77-8. PMID:11139256 doi:<77::AID-HUMU20>3.0.CO;2-H 10.1002/1098-1004(2001)17:1<77::AID-HUMU20>3.0.CO;2-H
- ↑ Timson DJ, Reece RJ. Functional analysis of disease-causing mutations in human galactokinase. Eur J Biochem. 2003 Apr;270(8):1767-74. PMID:12694189
- ↑ Sangiuolo F, Magnani M, Stambolian D, Novelli G. Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency. Hum Mutat. 2004 Apr;23(4):396. PMID:15024738 doi:10.1002/humu.9223
- ↑ Thoden JB, Timson DJ, Reece RJ, Holden HM. Molecular structure of human galactokinase: implications for type II galactosemia. J Biol Chem. 2005 Mar 11;280(10):9662-70. Epub 2004 Dec 7. PMID:15590630 doi:10.1074/jbc.M412916200
|
