Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T55610 Target Info
Target Name Hypoxia-inducible factor 1 alpha (HIF-1A)
Synonyms bHLHe78; Transcription factor HIF-1; PASD8; PAS domain-containing protein 8; Member of PAS protein 1; MOP1; Hypoxia-inducible transcription factor (HIF)-1; Hypoxia-inducible factor 1-alpha; Hypoxia-inducible factor 1 A; Hypoxia inducible factor 1; HIF1-alpha; HIF1 alpha; HIF-1alpha; HIF-1-alpha; HIF-1 alpha; Class E basic helix-loop-helix protein 78; Basic-helix-loop-helix-PAS protein MOP1; ARNT-interacting protein; ARNT interacting protein
Target Type Clinical trial Target
Gene Name HIF1A
UniProt ID
HIF1A_HUMAN
Ligand General Information  Top
Ligand Name 2-(carboxymethylamino)-2-oxoacetic acid Ligand Info
Canonical SMILES C(C(=O)O)NC(=O)C(=O)O
InChI 1S/C4H5NO5/c6-2(7)1-5-3(8)4(9)10/h1H2,(H,5,8)(H,6,7)(H,9,10)
InChIKey BIMZLRFONYSTPT-UHFFFAOYSA-N
PubChem Compound ID 3080614
Drug Binding Sites of Target  Top
PDB ID: 1H2M      Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide
Method X-ray diffraction Resolution 2.50 Å Mutation No [1]
PDB Sequence
LTSYDCEVNA
804
PILQGEELLR
820
AL
Residue
Distance (Å)
ASN803
4.852
Residue
Distance (Å)
PDB ID: 1H2K      Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide
Method X-ray diffraction Resolution 2.15 Å Mutation No [1]
PDB Sequence
LTSYDCEVNA
804
PILLQGEELL
819
RALD
Residue
Distance (Å)
ASN803
4.848
Residue
Distance (Å)
PDB ID: 5L9V      HIF prolyl hydroxylase 2 (PHD2-R281C/P317C) cross-linked to HIF-1alpha NODD-L397C/D412C and N-oxalylglycine (NOG) (complex-1)
Method X-ray diffraction Resolution 1.83 Å Mutation Yes [2]
PDB Sequence
DACTLLAPAA
404
GDTIISLCF
Residue
Distance (Å)
PRO402
2.420
Residue
Distance (Å)
PDB ID: 5LAS      HIF prolyl hydroxylase 2 (PHD2-R281C/P317C/R396T) cross-linked to HIF-1alpha NODD-L397C/D412C and N-oxalylglycine (NOG) (complex-3)
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [2]
PDB Sequence
DACTLLAPAA
404
GDTIISLCF
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OGA or .OGA2 or .OGA3 or :3OGA;style chemicals stick;color identity;select .C:402; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PRO402
2.445
Residue
Distance (Å)
PDB ID: 6YW3      HIF PROLYL HYDROXYLASE 2 (PHD2/ EGLN1) in complex with N-Oxalyl Glycine (NOG), HIF-1ALPHA CODD (556-574) and a RaPID-derived cyclic peptide 3C (14-mer)
Method X-ray diffraction Resolution 2.28 Å Mutation No [3]
PDB Sequence
DLEMLAPYIP
567
MDDDFQL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OGA or .OGA2 or .OGA3 or :3OGA;style chemicals stick;color identity;select .S:564; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PRO564
2.653
Residue
Distance (Å)
PDB ID: 5LA9      HIF prolyl hydroxylase 2 (PHD2-R281C/V314C) cross-linked to HIF-1alpha NODD-L397C/D412C and N-oxalylglycine (NOG) (complex-2)
Method X-ray diffraction Resolution 2.81 Å Mutation Yes [2]
PDB Sequence
DACTLLAPAA
404
GDTIISLCF
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OGA or .OGA2 or .OGA3 or :3OGA;style chemicals stick;color identity;select .C:402; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PRO402
2.440
Residue
Distance (Å)
PDB ID: 3HQR      PHD2:Mn:NOG:HIF1-alpha substrate complex
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [4]
PDB Sequence
DLEMLAPYIP
567
MDDDFQL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OGA or .OGA2 or .OGA3 or :3OGA;style chemicals stick;color identity;select .S:564; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PRO564
3.167
Residue
Distance (Å)
References  Top
REF 1 Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha. J Biol Chem. 2003 Jan 17;278(3):1802-6.
REF 2 Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Nat Commun. 2016 Aug 26;7:12673.
REF 3 Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2. Sci Rep. 2020 Dec 15;10(1):21964.
REF 4 Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases. Structure. 2009 Jul 15;17(7):981-9.

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