PDBsum entry 4bc5

Transferase

PDB id: 4bc5

Contents

Protein chain

524 a.a.

Ligands

5FX ×3

EDO

Waters ×739

PDB id:

4bc5

Name:

Transferase

Title:

Crystal structure of human d-xylulokinase in complex with inhibitor 5- deoxy-5-fluoro-d-xylulose

Structure:

Xylulose kinase. Chain: a, b, c. Synonym: d-xylulokinase, xylulokinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.98Å R-factor: 0.173 R-free: 0.192

Authors:

R.D.Bunker,K.M.Loomes,E.N.Baker

Key ref:

R.D.Bunker et al. (2013). Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism. J Biol Chem, 288, 1643-1652. PubMed id: 23179721

Date:

01-Oct-12 Release date: 28-Nov-12

Protein chains

O75191  (XYLB_HUMAN) -  Xylulose kinase from Homo sapiens

Seq: 536 a.a.

Struc: 524 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.17 - xylulokinase.
• Reaction: D-xylulose + ATP = D-xylulose 5-phosphate + ADP + H⁺

D-xylulose + ATP (Bound ligand (Het Group name = 5FX) matches with 81.82% similarity) = D-xylulose 5-phosphate + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Biol Chem 288:1643-1652 (2013)

PubMed id: 23179721

Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism.

R.D.Bunker, E.M.Bulloch, J.M.Dickson, K.M.Loomes, E.N.Baker.

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 K(m)(Xu) = 24 ± 3 μm and k(cat) = 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.