ISDA: 5AJY

Deposition Date 2015-02-27

Release Date 2015-04-22

Last Version Date 2024-05-08

Entry Detail

PDB ID:

5AJY

Keywords:

TRANSFERASE

Title:

Human PFKFB3 in complex with an indole inhibitor 4

Biological Source:

Source Organism(s):

HOMO SAPIENS (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.37 Å

R-Value Free:

0.21

R-Value Work:

0.19

R-Value Observed:

0.19

Space Group:

P 65 2 2

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:6-PHOSPHOFRUCTO-2-KINASE/FRUC
Gene (Uniprot):PFKFB3
Chain IDs:A
Chain Length:520
Number of Molecules:1
Biological Source:HOMO SAPIENS

UniProt ID:Q16875 Pfam ID:PF01591, PF00300 EC:2.7.1.105

Ligand Molecules

87T

F6P

PHS

PO4

Primary Citation

Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase Pfkfb3.

Boyd, S, Brookfield, J.L, Critchlow, S.E, Cumming, I.A, Curtis, N.J, Debreczeni, J, Degorce, S.L, Donald, C, Evans, N.J, Groombridge, S, Hopcroft, P, Jones, N.P, Kettle, J.G, Lamont, S, Lewis, H.J, Macfaull, P, Mcloughlin, S.B, Rigoreau, L.J.M, Smith, J.M, St-Gallay, S, Stock, J.K, Turnbull, A.P, Wheatley, E.R, Winter, J, Wingfield, J.Show

J.Med.Chem. 58 3611 ? (2015)

PMID: 25849762 DOI: 10.1021/ACS.JMEDCHEM.5B00352

Abstact

A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.

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Primary Citation of related structures

Abstact

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