PDBsum entry 1qw6

Oxidoreductase

PDB id: 1qw6

Contents

Protein chain

420 a.a. *

Ligands

HEM

H4B

3AR

Metals

_ZN

Waters ×280

* Residue conservation analysis

PDB id:

1qw6

Name:

Oxidoreductase

Title:

Rat neuronal nitric oxide synthase oxygenase domain in complex with n- omega-propyl-l-arg.

Structure:

Nitric-oxide synthase, brain. Chain: a. Fragment: residues 298-716. Synonym: nos, type i, neuronal nos, n-nos, nnos, constitutive nos, nc-nos, bnos. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: nos1 or bnos. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.10Å R-factor: 0.195 R-free: 0.243

Authors:

R.Fedorov,E.Hartmann,D.K.Ghosh,I.Schlichting

Key ref:

R.Fedorov et al. (2003). Structural basis for the specificity of the nitric-oxide synthase inhibitors W1400 and Nomega-propyl-L-Arg for the inducible and neuronal isoforms. J Biol Chem, 278, 45818-45825. PubMed id: 12954642 DOI: 10.1074/jbc.M306030200

Date:

01-Sep-03 Release date: 09-Dec-03

Protein chain

P29476  (NOS1_RAT) -  Nitric oxide synthase 1 from Rattus norvegicus

Seq: 1429 a.a.

Struc: 420 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.14.13.39 - nitric-oxide synthase (NADPH).
• Reaction: 2 L-arginine + 3 NADPH + 4 O2 + H⁺ = 2 L-citrulline + 2 nitric oxide + 3 NADP⁺ + 4 H2O

2 × L-arginine + 3 × NADPH (Bound ligand (Het Group name = 3AR) matches with 80.00% similarity) + 4 × O2 + H(+) = 2 × L-citrulline + 2 × nitric oxide + 3 × NADP(+) + 4 × H2O

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

reference

DOI no: 10.1074/jbc.M306030200

J Biol Chem 278:45818-45825 (2003)

PubMed id: 12954642

Structural basis for the specificity of the nitric-oxide synthase inhibitors W1400 and Nomega-propyl-L-Arg for the inducible and neuronal isoforms.

R.Fedorov, E.Hartmann, D.K.Ghosh, I.Schlichting.

ABSTRACT

The high level of amino acid conservation and structural similarity in the immediate vicinity of the substrate binding sites of the oxygenase domains of the nitric-oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, and nNOSoxy) make the interpretation of the structural basis of inhibitor isoform specificity a challenge and provide few clues for the design of new selective compounds. Crystal structures of iNOSoxy and nNOSoxy complexed with the inhibitors W1400 and Nomega-propyl-l-arginine provide a rationale for their isoform specificity. It involves differences outside the immediate active site as well as a conformational flexibility in the active site that allows the adoption of distinct conformations in response to interactions with the inhibitors. This flexibility is determined by isoform-specific residues outside the active site.

Selected figure(s)

Figure 1.
FIG. 1. F[obs] - F[calc] difference electron density omit maps contoured at 3 showing the inhibitors N -propyl-L-Arg (top) and W1400 (bottom) bound to nNOSoxy (left) and the two crystallographically independent molecules in the iNOSoxy crystal form (molecule 1 (middle); molecule 2 (right)).

Figure 2.
FIG. 2. A, comparison of the structures of the iNOSoxy (green) and nNOSoxy (gray) NPA complexes. There is one qualitatively different interaction in the nNOSoxy complex that originates ultimately from Asn-498 located in the substrate access channel. iNOSoxy has a threonine (T277) at this position. B, the view onto the heme plane shows the difference in the positioning of -strand S15 (F363 to W366, iNOS numbering) that makes up the back wall of the heme cavity. Asn-364 limits the space available for the propyl chain of NPA in iNOSoxy. C-E, for illustration, the cavity between the backwall and N of the bound L-Arg is shown (green mesh) and the NPA coordinates are superimposed on the corresponding L-Arg complexes. For eNOSoxy (Protein Data Bank code 4NSE [PDB] ), the coordinates of NPA of the nNOSoxy-NPA complex were used. In contrast to iNOSoxy (E), the cavity is rather large in nNOSoxy (C) and eNOSoxy (D), explaining the latter's good acceptance of inhibitors with bulky groups at the N position. F, -strand S15 in murine iNOSoxy (green), human iNOSoxy (gray), bovine eNOSoxy (violet), and human eNOSoxy (red) structures.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 45818-45825) copyright 2003.

Figures were selected by an automated process.