1wuu
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1wuu.gif|left|200px]] | [[Image:1wuu.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1wuu", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1wuu| PDB=1wuu | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''crystal structure of human galactokinase complexed with MgAMPPNP and galactose''' | '''crystal structure of human galactokinase complexed with MgAMPPNP and galactose''' | ||
| Line 33: | Line 30: | ||
[[Category: Thoden, J B.]] | [[Category: Thoden, J B.]] | ||
[[Category: Timson, D J.]] | [[Category: Timson, D J.]] | ||
| - | [[Category: | + | [[Category: Galactosemia]] |
| - | [[Category: | + | [[Category: Ghmp superfamily]] |
| - | [[Category: | + | [[Category: Kinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:09:58 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:09, 3 May 2008
crystal structure of human galactokinase complexed with MgAMPPNP and galactose
Contents |
Overview
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.
Disease
Known disease associated with this structure: Galactokinase deficiency with cataracts OMIM:[604313]
About this Structure
1WUU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 14:09:58 2008
