PDBsum entry 4gwc

Hydrolase

PDB id: 4gwc

Contents

Protein chain

313 a.a.

Metals

_ZN ×2

_MN ×4

Waters ×79

PDB id:

4gwc

Name:

Hydrolase

Title:

Crystal structure of mn2+2,zn2+-human arginase i

Structure:

Arginase-1. Chain: a, b. Fragment: human arginase i. Synonym: liver-type arginase, type i arginase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arg1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.90Å R-factor: 0.154 R-free: 0.221

Authors:

E.L.D'Antonio,Y.Hai,D.W.Christianson

Key ref:

E.L.D'Antonio et al. (2012). Structure and function of non-native metal clusters in human arginase I. Biochemistry, 51, 8399-8409. PubMed id: 23061982

Date:

01-Sep-12 Release date: 26-Sep-12

Protein chains

P05089  (ARGI1_HUMAN) -  Arginase-1 from Homo sapiens

Seq: 322 a.a.

Struc: 313 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.3.1 - arginase.
• Pathway: Urea Cycle and Arginine Biosynthesis
• Reaction: L-arginine + H2O = urea + L-ornithine
• Cofactor: Mn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 51:8399-8409 (2012)

PubMed id: 23061982

Structure and function of non-native metal clusters in human arginase I.

E.L.D'Antonio, Y.Hai, D.W.Christianson.

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.