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1wuu

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{{STRUCTURE_1wuu| PDB=1wuu | SCENE= }}
{{STRUCTURE_1wuu| PDB=1wuu | SCENE= }}
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'''crystal structure of human galactokinase complexed with MgAMPPNP and galactose'''
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===crystal structure of human galactokinase complexed with MgAMPPNP and galactose===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15590630 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15590630}}
==Disease==
==Disease==
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[[Category: Ghmp superfamily]]
[[Category: Ghmp superfamily]]
[[Category: Kinase]]
[[Category: Kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:14:34 2008''

Revision as of 16:14, 28 July 2008

Image:1wuu.png

Template:STRUCTURE 1wuu

Contents

crystal structure of human galactokinase complexed with MgAMPPNP and galactose

Template:ABSTRACT PUBMED 15590630

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

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