1dww

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spinqualitylabelsall models 1dww, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MURINE INDUCIBLE NITRIC OXIDE SYNTHASE OXYGENASE DIMER N-HYDROXYARGININE AND DIHYDROBIOPTERIN

Overview

The oxygenase domain of the inducible nitric oxide synthase (iNOSox;, residues 1-498) is a dimer that binds heme, L-arginine and, tetrahydrobiopterin (H(4)B) and is the site for nitric oxide synthesis. We, examined an N-terminal segment that contains a beta-hairpin hook, a zinc, ligation center and part of the H(4)B-binding site for its role in, dimerization, catalysis, and H(4)B and substrate interactions. Deletion, mutagenesis identified the minimum catalytic core and indicated that an, intact N-terminal beta-hairpin hook is essential. Alanine screening, mutagenesis of conserved residues in the hook revealed five positions, (K82, N83, D92, T93 and H95) where native properties were perturbed., Mutants fell into two classes: (i) incorrigible mutants that disrupt, side-chain hydrogen bonds and packing interactions with the iNOSox, C-terminus (N83, D92 and H95) and cause permanent defects in homodimer, formation, H(4)B binding and activity; and (ii) reformable mutants that, destabilize interactions of the residue main chain (K82 and T93) with the, C-terminus and cause similar defects that were reversible with high, concentrations of H(4)B. Heterodimers comprised of a hook-defective iNOSox, mutant subunit and a full-length iNOS subunit were active in almost all, cases. This suggests a mechanism whereby N-terminal hooks exchange between, subunits in solution to stabilize the dimer.

About this Structure

1DWW is a Single protein structure of sequence from Mus musculus with ZN, SO4, HEM, H2B and HAR as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.

Reference

Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook and pterin-binding segment in dimerization and tetrahydrobiopterin interaction., Ghosh DK, Crane BR, Ghosh S, Wolan D, Gachhui R, Crooks C, Presta A, Tainer JA, Getzoff ED, Stuehr DJ, EMBO J. 1999 Nov 15;18(22):6260-70. PMID:10562538

Page seeded by OCA on Tue Nov 20 13:38:53 2007