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1wuu

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Revision as of 03:32, 11 September 2015

crystal structure of human galactokinase complexed with MgAMPPNP and galactose

Structural highlights

1wuu is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Gene:	GALK1 (HUMAN)
Activity:	Galactokinase, with EC number 2.7.1.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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.

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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wuu"

@@ Line 2: / Line 2: @@
 <StructureSection load='1wuu' size='340' side='right' caption='[[1wuu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wuu]] is a 4 chain structure with sequence from [http://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 [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 [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>
 </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>
 <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='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 Homo sapiens])</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='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://www.rcsb.org/pdb/explore.do?structureId=1wuu RCSB], [http://www.ebi.ac.uk/pdbsum/1wuu PDBsum]</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>
 == Disease ==
@@ Line 31: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1wuu" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Galactokinase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Holden, H M]]
 [[Category: Reece, R J]]

1wuu

From Proteopedia

Revision as of 03:32, 11 September 2015

crystal structure of human galactokinase complexed with MgAMPPNP and galactose

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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