2WA4

FACTOR INHIBITING HIF-1 ALPHA WITH N,3-dihydroxybenzamide

Summary for 2WA4

• Entry DOI: 10.2210/pdb2wa4/pdb
• Related: 1H2K 1H2L 1H2M 1H2N 1IZ3 1MZE 1MZF 1YCI 2CGN 2CGO 2W0X 2WA3
• Descriptor: HYPOXIA-INDUCIBLE FACTOR 1-ALPHA INHIBITOR, FE (II) ION, N,3-DIHYDROXYBENZAMIDE, ... (5 entities in total)
• Functional Keywords: hydroxylase, dioxygenase, transcription, oxidoreductase, transcription activator/inhibitor, hypoxia
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: Q9NWT6
• Total number of polymer chains: 1
• Total formula weight: 40786.46

Authors

Conejo-Garcia, A.,Lienard, B.M.R.,Clifton, I.J.,McDonough, M.A.,Schofield, C.J. (deposition date: 2009-02-02, release date: 2010-04-21, Last modification date: 2023-12-13)

Primary citation

Conejo-Garcia, A.,McDonough, M.A.,Loenarz, C.,McNeill, L.A.,Hewitson, K.S.,Ge, W.,Lienard, B.M.,Schofield, C.J.,Clifton, I.J.
Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor.
Bioorg. Med. Chem. Lett., 20:6125-6128, 2010

PubMed Abstract: Aromatic analogues of the 2-oxoglutarate co-substrate of the hypoxia-inducible factor hydroxylases are shown to bind at the active site iron: Pyridine-2,4-dicarboxylate binds as anticipated with a single molecule chelating the iron in a bidentate manner. The binding mode of a hydroxamic acid analogue, at least in the crystalline state, is unusual because two molecules of the inhibitor are observed at the active site and partial displacement of the iron binding aspartyl residue was observed.

PubMed: 20822901
DOI: 10.1016/j.bmcl.2010.08.032

Experimental method

X-RAY DIFFRACTION (2.5 Å)