Literature summary for 3.4.11.3 extracted from

Mpakali, A.; Saridakis, E.; Harlos, K.; Zhao, Y.; Kokkala, P.; Georgiadis, D.; Giastas, P.; Papakyriakou, A.; Stratikos, E.
ligand-induced conformational change of insulin-regulated aminopeptidase insights on catalytic mechanism and active site plasticity (2017), J. Med. Chem., 60, 2963-2972 .

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with inhibitory peptide [(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid, sitting drop vapor diffusion, mixing of 5 mg/ml protein in 150 mM NaCl, and 10 mM HEPES, pH 7.5, with 100 nl of crystallization solution containing 18.8% w/v PEG 20000, 37.6% v/v PEG monomethyl ether 500, 50.2 mM bicine, 43.8 mM Trizma base, pH 8.5, and 0.282 M of each of sodium fluoride, sodium bromide, and sodium iodide, 21°C, method optimization, X-ray diffraction structure determination and analysis at 2.53 A resolution, molecular replacement using the highly homologous aminopeptidase ERAP1 structure (PDB ID 2YD0) as a search model, and modelling	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in complex with inhibitory peptide [(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid, sitting drop vapor diffusion, mixing of 5 mg/ml protein in 150 mM NaCl, and 10 mM HEPES, pH 7.5, with 100 nl of crystallization solution containing 18.8% w/v PEG 20000, 37.6% v/v PEG monomethyl ether 500, 50.2 mM bicine, 43.8 mM Trizma base, pH 8.5, and 0.282 M of each of sodium fluoride, sodium bromide, and sodium iodide, 21°C, method optimization, X-ray diffraction structure determination and analysis at 2.53 A resolution, molecular replacement using the highly homologous aminopeptidase ERAP1 structure (PDB ID 2YD0) as a search model, and modelling

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
ethyl 2-acetamido-7-hydroxy-4-(3-quinolinyl)-4H-chromene-3-carboxylate	HFI-437	Homo sapiens
additional information	enzyme IRAP undergoes a conformational change upon inhibitor binding, docking study. Analysis of structural determinants for inhibitor selectivity, overview. Significant affinity is generated by structural elements common to all homologous enzymes: the active-site Zn(II) atom, the catalytic Tyr549 and Glu465, N-terminus recognition by Glu295, Glu431, and Glu487, and the S1 specificity residue Phe544	Homo sapiens
[(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid	i.e. DG026, a phosphinic pseudotripeptide that acts as very potent inhibitor of IRAP. DG026 is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells but leave ERAP1-dependent cross-presentation unaffected. Enzyme binding structure determination and analysis, overview	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Zn2+	active site-bound	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9UIQ6	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
dendritic cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
insulin-regulated aminopeptidase	-	Homo sapiens
IRAP	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	peptide inhibitor [(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells	down

General Information

General Information	Comment	Organism
malfunction	peptide inhibitor DG026 is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells but leave ERAP1-dependent cross-presentation unaffected	Homo sapiens
additional information	enzyme IRAP undergoes a conformational change upon inhibitor binding	Homo sapiens