4BQX

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with Mn(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)

Summary for 4BQX

• Entry DOI: 10.2210/pdb4bqx/pdb
• Related: 4BQW 4BQY
• Descriptor: EGL NINE HOMOLOG 1, MANGANESE (II) ION, N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE, ... (4 entities in total)
• Functional Keywords: oxidoreductase, 2-oxoglutarate, dioxygenase, egln, oxygenase, dna-binding, transcription, dsbh, facial triad, asparaginyl/ aspartyl hydroxylase, transcription and epigenetic regulation, signaling, development, cell structure, ard, beta-hydroxylation, transcription activator/inhibitor, s-nitrosylation
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 28432.54

Authors

Chowdhury, R.,Schofield, C.J. (deposition date: 2013-06-03, release date: 2013-06-19, Last modification date: 2024-10-09)

Primary citation

Chowdhury, R.,Candela-Lena, J.I.,Chan, M.C.,Greenald, D.J.,Yeoh, K.K.,Tian, Y.M.,McDonough, M.A.,Tumber, A.,Rose, N.R.,Conejo-Garcia, A.,Demetriades, M.,Mathavan, S.,Kawamura, A.,Lee, M.K.,van Eeden, F.,Pugh, C.W.,Ratcliffe, P.J.,Schofield, C.J.
Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases.
ACS Chem. Biol., 8:1488-1496, 2013

PubMed Abstract: The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic, cellular profiling, and animal studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in animals.

PubMed: 23683440
DOI: 10.1021/cb400088q

Experimental method

X-RAY DIFFRACTION (1.79 Å)