7k4h

Human Arginase 1 in complex with compound 04.Human Arginase 1 in complex with compound 04.

Structural highlights

7k4h is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ARGI1_HUMAN Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.^[1] ^[2]

Function

ARGI1_HUMAN

Publication Abstract from PubMed

Comprehensive synthetic strategies afforded a diverse set of structurally unique bicyclic proline-containing arginase inhibitors with a high degree of three-dimensionality. The analogs that favored the Cgamma-exo conformation of the proline improved the arginase potency over the initial lead. The novel synthetic strategies reported here not only enable access to previously unknown stereochemically complex proline derivatives but also provide a foundation for the future synthesis of bicyclic proline analogs, which incorporate inherent three-dimensional character into building blocks, medicine, and catalysts and could have a profound impact on the conformation of proline-containing peptides and macrocycles.

Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.,Li D, Zhang H, Lyons TW, Lu M, Achab A, Pu Q, Childers M, Mitcheltree MJ, Wang J, Martinot TA, McMinn SE, Sloman DL, Palani A, Beard A, Nogle L, Gathiaka S, Sauri J, Kim HY, Adpressa D, Spacciapoli P, Miller JR, Palte RL, Lesburg CA, Cumming J, Fischer C ACS Med Chem Lett. 2021 Oct 13;12(11):1678-1688. doi:, 10.1021/acsmedchemlett.1c00258. eCollection 2021 Nov 11. PMID:34795856^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Uchino T, Haraguchi Y, Aparicio JM, Mizutani N, Higashikawa M, Naitoh H, Mori M, Matsuda I. Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. Am J Hum Genet. 1992 Dec;51(6):1406-12. PMID:1463019
↑ Uchino T, Snyderman SE, Lambert M, Qureshi IA, Shapira SK, Sansaricq C, Smit LM, Jakobs C, Matsuda I. Molecular basis of phenotypic variation in patients with argininemia. Hum Genet. 1995 Sep;96(3):255-60. PMID:7649538
↑ Li D, Zhang H, Lyons TW, Lu M, Achab A, Pu Q, Childers M, Mitcheltree MJ, Wang J, Martinot TA, McMinn SE, Sloman DL, Palani A, Beard A, Nogle L, Gathiaka S, Sauri J, Kim HY, Adpressa D, Spacciapoli P, Miller JR, Palte RL, Lesburg CA, Cumming J, Fischer C. Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors. ACS Med Chem Lett. 2021 Oct 13;12(11):1678-1688. doi:, 10.1021/acsmedchemlett.1c00258. eCollection 2021 Nov 11. PMID:34795856 doi:http://dx.doi.org/10.1021/acsmedchemlett.1c00258

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Uchino T, Haraguchi Y, Aparicio JM, Mizutani N, Higashikawa M, Naitoh H, Mori M, Matsuda I. Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. Am J Hum Genet. 1992 Dec;51(6):1406-12. PMID:1463019

[2] Uchino T, Snyderman SE, Lambert M, Qureshi IA, Shapira SK, Sansaricq C, Smit LM, Jakobs C, Matsuda I. Molecular basis of phenotypic variation in patients with argininemia. Hum Genet. 1995 Sep;96(3):255-60. PMID:7649538

[3] Li D, Zhang H, Lyons TW, Lu M, Achab A, Pu Q, Childers M, Mitcheltree MJ, Wang J, Martinot TA, McMinn SE, Sloman DL, Palani A, Beard A, Nogle L, Gathiaka S, Sauri J, Kim HY, Adpressa D, Spacciapoli P, Miller JR, Palte RL, Lesburg CA, Cumming J, Fischer C. Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors. ACS Med Chem Lett. 2021 Oct 13;12(11):1678-1688. doi:, 10.1021/acsmedchemlett.1c00258. eCollection 2021 Nov 11. PMID:34795856 doi:http://dx.doi.org/10.1021/acsmedchemlett.1c00258

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