PDBsum entry 3wxl

Transferase

PDB id: 3wxl

Contents

Protein chains

513 a.a.

Ligands

GOL ×6

ADP ×5

Metals

_MG ×2

Waters ×1092

PDB id:

3wxl

Name:

Transferase

Title:

Crystal structure of trypanosoma brucei gambiense glycerol kinase complex with adp, mg2+, and glycerol

Structure:

Glycerol kinase. Chain: a, b, c, d. Engineered: yes

Source:

Trypanosoma brucei gambiense. Organism_taxid: 31285. Gene: gk. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.214 R-free: 0.254

Authors:

E.O.Balogun,D.K.Inaoka,T.Shiba,Y.Kido,C.Tsuge,T.Nara,T.Aoki,T.Honma, A.Tanaka,M.Inoue,S.Matsuoka,P.A.M.Michels,K.Kita,S.Harada

Key ref:

E.O.Balogun et al. (2014). Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase. Mol Microbiol, 94, 1315-1329. PubMed id: 25315291 DOI: 10.1111/mmi.12831

Date:

01-Aug-14 Release date: 24-Dec-14

Protein chains

D3KVM3  (D3KVM3_TRYBG) -  glycerol kinase from Trypanosoma brucei gambiense

Seq: 512 a.a.

Struc: 513 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.30 - glycerol kinase.
• Reaction: glycerol + ATP = sn-glycerol 3-phosphate + ADP + H⁺

glycerol + ATP (Bound ligand (Het Group name = GOL) corresponds exactly) = sn-glycerol 3-phosphate (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

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

reference

DOI no: 10.1111/mmi.12831

Mol Microbiol 94:1315-1329 (2014)

PubMed id: 25315291

Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase.

E.O.Balogun, D.K.Inaoka, T.Shiba, Y.Kido, C.Tsuge, T.Nara, T.Aoki, T.Honma, A.Tanaka, M.Inoue, S.Matsuoka, P.A.Michels, K.Kita, S.Harada.

ABSTRACT

The glycerol kinase (GK) of African human trypanosomes is compartmentalized in their glycosomes. Unlike the host GK, which under physiological conditions catalyzes only the forward reaction (ATP-dependent glycerol phosphorylation), trypanosome GK can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, GK is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure-based catalytic differences also contribute. To investigate this lack of information, the X-ray crystal structure of this protein was determined up to 1.90 Å resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure-guided mutagenesis suggests that the trypanosome GK is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non-conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome GK-specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s).