7K4I

Human Arginase 1 in complex with compound 06.

Summary for 7K4I

• Entry DOI: 10.2210/pdb7k4i/pdb
• Descriptor: Arginase-1, MANGANESE (II) ION, 3-[(1~{S},2~{S},5~{R})-2-carboxy-6-thia-3-azabicyclo[3.2.0]heptan-1-yl]propyl-$l^{3}-oxidanyl-bis(oxidanyl)boranuide, ... (4 entities in total)
• Functional Keywords: arginase, hydrolase, arginine, urea cycle, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 210911.20

Authors

Palte, R.L. (deposition date: 2020-09-15, release date: 2021-10-06, Last modification date: 2023-10-18)

Primary citation

Li, D.,Zhang, H.,Lyons, T.W.,Lu, M.,Achab, A.,Pu, Q.,Childers, M.,Mitcheltree, M.J.,Wang, J.,Martinot, T.A.,McMinn, S.E.,Sloman, D.L.,Palani, A.,Beard, A.,Nogle, L.,Gathiaka, S.,Sauri, J.,Kim, H.Y.,Adpressa, D.,Spacciapoli, P.,Miller, J.R.,Palte, R.L.,Lesburg, C.A.,Cumming, J.,Fischer, C.
Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.
Acs Med.Chem.Lett., 12:1678-1688, 2021

PubMed Abstract: 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 Cγ-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.

PubMed: 34795856
DOI: 10.1021/acsmedchemlett.1c00258

Experimental method

X-RAY DIFFRACTION (1.98 Å)