dc.contributor.author |
Bunker, RD |
|
dc.contributor.author |
Bulloch, EMM |
|
dc.contributor.author |
Dickson, JMJ |
|
dc.contributor.author |
Loomes, KM |
|
dc.contributor.author |
Baker, EN |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2022-06-13T23:06:52Z |
|
dc.date.available |
2022-06-13T23:06:52Z |
|
dc.date.issued |
2013-01-18 |
|
dc.identifier.citation |
(2013). Journal of Biological Chemistry, 288(3), 1643-1652. |
|
dc.identifier.issn |
0021-9258 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/59809 |
|
dc.description.abstract |
D-Xylulokinase (XK; EC 2.7.1.17) catalyzes the ATP-dependent phosphorylation of D-xylulose (Xu) to produce xylulose 5-phosphate (Xu5P). In mammals, XK is the last enzyme in the glucuronate-xylulose pathway, active in the liver and kidneys, and is linked through its product Xu5P to the pentose-phosphate pathway. XK may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis. We have expressed the product of a putative human XK gene and identified it as the authentic human D-xylulokinase (hXK). NMR studies with a variety of sugars showed that hXK acts only on D-xylulose, and a coupled photometric assay established its key kinetic parameters as Km(Xu) = 24 ± 3 μM and kcat = 35 ± 5 s−1. Crystal structures were determined for hXK, on its own and in complexes with Xu, ADP, and a fluorinated inhibitor. These reveal that hXK has a two-domain fold characteristic of the sugar kinase/hsp70/actin superfamily, with glycerol kinase as its closest relative. Xu binds to domain-I and ADP to domain-II, but in this open form of hXK they are 10 Å apart, implying that a large scale conformational change is required for catalysis. Xu binds in its linear keto-form, sandwiched between a Trp side chain and polar side chains that provide exquisite hydrogen bonding recognition. The hXK structure provides a basis for the design of specific inhibitors with which to probe its roles in sugar metabolism and metabolic disease. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Elsevier BV |
|
dc.relation.ispartofseries |
Journal of Biological Chemistry |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Humans |
|
dc.subject |
Escherichia coli |
|
dc.subject |
Phosphotransferases (Alcohol Group Acceptor) |
|
dc.subject |
Xylulose |
|
dc.subject |
Pentosephosphates |
|
dc.subject |
Recombinant Proteins |
|
dc.subject |
Adenosine Diphosphate |
|
dc.subject |
Crystallography, X-Ray |
|
dc.subject |
Magnetic Resonance Spectroscopy |
|
dc.subject |
Gene Expression |
|
dc.subject |
Catalytic Domain |
|
dc.subject |
Protein Structure, Secondary |
|
dc.subject |
Protein Structure, Tertiary |
|
dc.subject |
Substrate Specificity |
|
dc.subject |
Kinetics |
|
dc.subject |
Hydrogen Bonding |
|
dc.subject |
Models, Molecular |
|
dc.subject |
Digestive Diseases |
|
dc.subject |
Liver Disease |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
1.1 Normal biological development and functioning |
|
dc.subject |
Generic health relevance |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Biochemistry & Molecular Biology |
|
dc.subject |
ELEMENT-BINDING PROTEIN |
|
dc.subject |
RESPONSE ELEMENT |
|
dc.subject |
GLYCEROL KINASE |
|
dc.subject |
ESCHERICHIA-COLI |
|
dc.subject |
SACCHAROMYCES-CEREVISIAE |
|
dc.subject |
ESSENTIAL PENTOSURIA |
|
dc.subject |
CRYSTAL-STRUCTURES |
|
dc.subject |
DATA QUALITY |
|
dc.subject |
GLUCOSE |
|
dc.subject |
LIVER |
|
dc.subject |
0601 Biochemistry and Cell Biology |
|
dc.subject |
Biomedical |
|
dc.subject |
03 Chemical Sciences |
|
dc.subject |
06 Biological Sciences |
|
dc.subject |
11 Medical and Health Sciences |
|
dc.title |
Structure and Function of Human Xylulokinase, an Enzyme with Important Roles in Carbohydrate Metabolism |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1074/jbc.M112.427997 |
|
pubs.issue |
3 |
|
pubs.begin-page |
1643 |
|
pubs.volume |
288 |
|
dc.date.updated |
2022-05-02T09:00:21Z |
|
dc.rights.holder |
Copyright: The American Society for Biochemistry and Molecular Biology |
en |
dc.identifier.pmid |
23179721 (pubmed) |
|
pubs.author-url |
http://www.ncbi.nlm.nih.gov/pubmed/23179721 |
|
pubs.end-page |
1652 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
|
pubs.elements-id |
365269 |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
dc.identifier.eissn |
1083-351X |
|
dc.identifier.pii |
S0021-9258(20)46578-0 |
|
pubs.record-created-at-source-date |
2022-05-02 |
|
pubs.online-publication-date |
2012-11-23 |
|