PDBsum entry 1hqh

Hydrolase

PDB id: 1hqh

Contents

Protein chains

314 a.a. *

Ligands

NNH ×3

Metals

_MN ×6

Waters ×21

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Mechanistic and metabolic inferences from the binding of substrate analogues and products to arginase.
• Authors: J.D.Cox, E.Cama, D.M.Colleluori, S.Pethe, J.L.Boucher, D.Mansuy, D.E.Ash, D.W.Christianson.
• Ref.: Biochemistry, 2001, 40, 2689-2701. [DOI no: 10.1021/bi002318+]
• PubMed id: 11258880

Abstract

Arginase is a binuclear Mn(2+) metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. X-ray crystal structures of arginase complexed to substrate analogues N(omega)-hydroxy-L-arginine and N(omega)-hydroxy-nor-L-arginine, as well as the products L-ornithine and urea, complete a set of structural "snapshots" along the reaction coordinate of arginase catalysis when interpreted along with the X-ray crystal structure of the arginase-transition-state analogue complex described in Kim et al. [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, Jr., S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Taken together, these structures render important insight on the structural determinants of tight binding inhibitors. Furthermore, we demonstrate for the first time the structural mechanistic link between arginase and NO synthase through their respective complexes with N(omega)-hydroxy-L-arginine. That N(omega)-hydroxy-L-arginine is a catalytic intermediate for NO synthase and an inhibitor of arginase reflects the reciprocal metabolic relationship between these two critical enzymes of L-arginine catabolism.