Arginase I

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1244

Nomenclature: Arginase I

Abbreviated Name: ARG1

Family: Arginase

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	322	6q23.2	ARG1	arginase 1
Mouse	-	323	10 A4	Arg1	arginase, liver
Rat	-	323	1p12	Arg1	arginase 1

Previous and Unofficial Names
Liver arginase \| AI type I arginase \| PGIF \| cytosolic arginase \| arginase

Database Links
Alphafold	P05089 (Hs), Q61176 (Mm), P07824 (Rn)
BRENDA	3.5.3.1
ChEMBL Target	CHEMBL1075097 (Hs), CHEMBL4630836 (Mm), CHEMBL3232699 (Rn)
Ensembl Gene	ENSG00000118520 (Hs), ENSMUSG00000019987 (Mm), ENSRNOG00000013304 (Rn)
Entrez Gene	383 (Hs), 11846 (Mm), 29221 (Rn)
Human Protein Atlas	ENSG00000118520 (Hs)
KEGG Enzyme	3.5.3.1
KEGG Gene	hsa:383 (Hs), mmu:11846 (Mm), rno:29221 (Rn)
OMIM	608313 (Hs)
Pharos	P05089 (Hs)
SynPHARM	83383 (in complex with compound 9 [PMID: 23472952])
UniProtKB	P05089 (Hs), Q61176 (Mm), P07824 (Rn)
Wikipedia	ARG1 (Hs)

Selected 3D Structures

Image of receptor 3D structure from RCSB PDB

Description:	Crystal structure of human Arginase-1 complexed with inhibitor 9.
PDB Id:	4HWW
Ligand:	compound 9 [PMID: 23472952]
Resolution:	1.3Å
Species:	Human
References:	4

Enzyme Reaction

EC Number: 3.5.3.1
	Description	Reaction	Reference
		L-arginine + H₂O <=> L-ornithine + urea

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Inhibitors

Key to terms and symbols

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Ligand		Sp.	Action	Value	Parameter	Reference
2(S)-amino-6-boronohexanoic acid		Hs	Inhibition	8.3	pK_d	2
⤷	pK_d 8.3 (K_d 5x10^-9 M) [2]
A1P		Hs	Inhibition	5.7	pK_d	3
⤷	pK_d 5.7 (K_d 2x10^-6 M) [3] Description: Dissociation constant measured using surface plasmon resonance assay.
A1P		Hs	Inhibition	5.4	pK_i	3
⤷	pK_i 5.4 (K_i 4x10^-6 M) [3] Description: Measured using an enzyme kinetics assay.
compound 9 [PMID: 23472952]		Hs	Inhibition	6.7	pIC₅₀	4
⤷	pIC₅₀ 6.7 (IC₅₀ 2.23x10^-7 M) [4]

Immunopharmacology Comments
The role of ARG1 in immuno-oncology is reviewed in [1].

Immunopharmacology Comments

The role of ARG1 in immuno-oncology is reviewed in [1].

Immuno Process Associations

Immuno Process:

T cell (activation)

Immuno Process:

B cell (activation)

Immuno Process:

Immune regulation

Immuno Process:

Chemotaxis & migration

Immuno Process:

Inflammation

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Cellular signalling

Immuno Process:

Cytokine production & signalling

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. Baggio R, Elbaum D, Kanto ZF, Carroll PJ, Cavalli RC, Ash DE, Christianson DW. (1997) Inhibition of Mn2⁺2-Arginase by Borate Leads to the Design of a Transition State Analogue Inhibitor, 2(S)-Amino-6-boronohexanoic Acid. J Am Chem Soc, 119 (34): 8107–8108.

3. Ilies M, Di Costanzo L, North ML, Scott JA, Christianson DW. (2010) 2-aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I. J Med Chem, 53 (10): 4266-76. [PMID:20441173]

4. Van Zandt MC, Whitehouse DL, Golebiowski A, Ji MK, Zhang M, Beckett RP, Jagdmann GE, Ryder TR, Sheeler R, Andreoli M et al.. (2013) Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury. J Med Chem, 56 (6): 2568-80. [PMID:23472952]