3KV2

HIGH RESOLUTION STRUCTURE OF HUMAN ARGINASE I IN COMPLEX WITH THE STRONG INHIBITOR N(omega)-hydroxy-nor-L-arginine (nor-NOHA)

Summary for 3KV2

• Entry DOI: 10.2210/pdb3kv2/pdb
• Descriptor: Arginase-1, MANGANESE (II) ION, NOR-N-OMEGA-HYDROXY-L-ARGININE, ... (4 entities in total)
• Functional Keywords: strong inhibitor, nor-noha, arginase, high resolution, alternative splicing, arginine metabolism, cytoplasm, disease mutation, hydrolase, manganese, metal-binding, phosphoprotein, polymorphism, urea cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P05089
• Total number of polymer chains: 2
• Total formula weight: 70131.86

Authors

Di Costanzo, L.,Christianson, D.W. (deposition date: 2009-11-28, release date: 2009-12-22, Last modification date: 2023-09-06)

Primary citation

Di Costanzo, L.,Ilies, M.,Thorn, K.J.,Christianson, D.W.
Inhibition of human arginase I by substrate and product analogues.
Arch.Biochem.Biophys., 496:101-108, 2010

PubMed Abstract: Human arginase I is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to generate L-ornithine and urea. We demonstrate that N-hydroxy-L-arginine (NOHA) binds to this enzyme with K(d)=3.6 microM, and nor-N-hydroxy-L-arginine (nor-NOHA) binds with K(d)=517 nM (surface plasmon resonance) or K(d) approximately 50 nM (isothermal titration calorimetry). Crystals of human arginase I complexed with NOHA and nor-NOHA afford 2.04 and 1.55 A resolution structures, respectively, which are significantly improved in comparison with previously-determined structures of the corresponding complexes with rat arginase I. Higher resolution structures clarify the binding interactions of the inhibitors. Finally, the crystal structure of the complex with L-lysine (K(d)=13 microM) is reported at 1.90 A resolution. This structure confirms the importance of hydrogen bond interactions with inhibitor alpha-carboxylate and alpha-amino groups as key specificity determinants of amino acid recognition in the arginase active site.

PubMed: 20153713
DOI: 10.1016/j.abb.2010.02.004

Experimental method

X-RAY DIFFRACTION (1.55 Å)