PDBsum entry: 1nsi

Oxidoreductase

PDB id: 1nsi

Contents

Protein chains

420 a.a. *

Ligands

SO4 ×9

HEM ×4

H4B ×4

ARG ×4

GOL ×4

Metals

_ZN ×2

Waters ×295

* Residue conservation analysis

PDB id:

1nsi

Name:

Oxidoreductase

Title:

Human inducible nitric oxide synthase, zn-bound, l-arg compl

Structure:

Protein (nitric oxide synthase). Chain: a, b, c, d. Fragment: heme domain. Synonym: inos. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: adenocarcinoma dld-1. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.55Å R-factor: 0.209 R-free: 0.243

Authors:

H.Li,C.S.Raman,C.B.Glaser,E.Blasko,T.A.Young,J.F.Parkinson,M T.L.Poulos

Key ref:

H.Li et al. (1999). Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. J Biol Chem, 274, 21276-21284. PubMed id: 10409685 DOI: 10.1074/jbc.274.30.21276

Date:

10-Jan-99 Release date: 07-Jan-00

Protein chains

P35228  (NOS2_HUMAN) -  Nitric oxide synthase, inducible

Seq: 1153 a.a.

Struc: 420 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.13.39 - Nitric-oxide synthase.
• Reaction: L-arginine + n NADPH + n H⁺ + m O₂ = citrulline + nitric oxide + n NADP⁺

L-arginine (Bound ligand (Het Group name = ARG) corresponds exactly) + n NADPH + n H(+) + m O(2) = citrulline + nitric oxide + n NADP(+)

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

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation-reduction process (2 terms)
• Biochemical function: calmodulin binding (7 terms)

reference

DOI no: 10.1074/jbc.274.30.21276

J Biol Chem 274:21276-21284 (1999)

PubMed id: 10409685

Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase.

H.Li, C.S.Raman, C.B.Glaser, E.Blasko, T.A.Young, J.F.Parkinson, M.Whitlow, T.L.Poulos.

ABSTRACT

The crystal structures of the heme domain of human inducible nitric-oxide synthase (NOS-2) in zinc-free and -bound states have been solved. In the zinc-free structure, two symmetry-related cysteine residues form a disulfide bond. In the zinc-bound state, these same two cysteine residues form part of a zinc-tetrathiolate (ZnS(4)) center indistinguishable from that observed in the endothelial isoform (NOS-3). As in NOS-3, ZnS(4) plays a key role in stabilizing intersubunit contacts and in maintaining the integrity of the cofactor (tetrahydrobiopterin) binding site of NOS-2. A comparison of NOS-2 and NOS-3 structures illustrates the conservation of quaternary structure, tertiary topology, and substrate and cofactor binding sites, in addition to providing insights on isoform-specific inhibitor design. The structural comparison also reveals that pterin binding does not preferentially stabilize the dimer interface of NOS-2 over NOS-3.

Selected figure(s)

Figure 3.
Fig. 3. Superimposition of the zinc-free (magenta) and -bound (gray) human NOS-2 heme domain structures showing a peptide flip involving carbonyl group of Gly^117, which results in a lengthening of the hydrogen bond from the carbonyl oxygen of Ser^118 to the dihydroxypropyl side chain of H[4]B.

Figure 7.
Fig. 7. Extensive hydrogen-bonding interactions between isoform-selective inhibitor, N-(5(R)-amino-6,7-dihydroxyheptyl)ethanimidamide, and human NOS-2 as manually modeled in the crystal structure. Hydrogen bonds are drawn as dashed lines. The key difference is the inability of Asn^368 in NOS-3 to accept a hydrogen bond from the inhibitor.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 21276-21284) copyright 1999.

Figures were selected by an automated process.