4GSV

Crystal Structure of the Ni2+2-Human Arginase I-ABH complex

Summary for 4GSV

• Entry DOI: 10.2210/pdb4gsv/pdb
• Related: 2AEB 3THH 4GSM 4GSZ
• Descriptor: Arginase-1, NICKEL (II) ION, 2(S)-AMINO-6-BORONOHEXANOIC ACID, ... (4 entities in total)
• Functional Keywords: arginase fold, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P05089
• Total number of polymer chains: 2
• Total formula weight: 70178.53

Authors

D'Antonio, E.L.,Hai, Y.,Christianson, D.W. (deposition date: 2012-08-28, release date: 2012-09-26, Last modification date: 2023-09-13)

Primary citation

D'Antonio, E.L.,Hai, Y.,Christianson, D.W.
Structure and function of non-native metal clusters in human arginase I.
Biochemistry, 51:8399-8409, 2012

PubMed Abstract: Various binuclear metal ion clusters and complexes have been reconstituted in crystalline human arginase I by removing the Mn(2+)(2) cluster of the wild-type enzyme with metal chelators and subsequently soaking the crystalline apoenzyme in buffer solutions containing NiCl(2) or ZnCl(2). X-ray crystal structures of these metal ion variants are correlated with catalytic activity measurements that reveal differences resulting from metal ion substitution. Additionally, treatment of crystalline Mn(2+)(2)-human arginase I with Zn(2+) reveals for the first time the structural basis for inhibition by Zn(2+), which forms a carboxylate-histidine-Zn(2+) triad with H141 and E277. The imidazole side chain of H141 is known to be hyper-reactive, and its chemical modification or mutagenesis is known to similarly compromise catalysis. The reactive substrate analogue 2(S)-amino-6-boronohexanoic acid (ABH) binds as a tetrahedral boronate anion to Mn(2+)(2), Co(2+)(2), Ni(2+)(2), and Zn(2+)(2) clusters in human arginase I, and it can be stabilized by a third inhibitory Zn(2+) ion coordinated by H141. Because ABH binds as an analogue of the tetrahedral intermediate and its flanking transition states in catalysis, this implies that the various metallo-substituted enzymes are capable of some level of catalysis with an actual substrate. Accordingly, we establish the following trend for turnover number (k(cat)) and catalytic efficiency (k(cat)/K(M)): Mn(2+) > Ni(2+) ≈ Co(2+) ≫ Zn(2+). Therefore, Mn(2+) is required for optimal catalysis by human arginase I.

PubMed: 23061982
DOI: 10.1021/bi301145n

Experimental method

X-RAY DIFFRACTION (1.48 Å)