PDBsum entry 4ug9

Oxidoreductase

PDB id: 4ug9

Contents

Protein chain

362 a.a.

Ligands

HEM

1EW

GOL

Metals

_CL

Waters ×331

PDB id:

4ug9

Name:

Oxidoreductase

Title:

Structure of bacillus subtilis nitric oxide synthase in complex with 6,6'-((4-(3-aminopropyl)benzene-1,3-diyl)diethane-2,1-diyl)bis(4- methylpyridin-2-amine)

Structure:

Nitric oxide synthase oxygenase. Chain: a. Synonym: nosoxy-like protein. Engineered: yes. Mutation: yes

Source:

Bacillus subtilis. Organism_taxid: 224308. Strain: 168. Atcc: 23857. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.84Å R-factor: 0.165 R-free: 0.208

Authors:

J.K.Holden,T.L.Poulos

Key ref:

J.K.Holden et al. (2015). Inhibitor Bound Crystal Structures of Bacterial Nitric Oxide Synthase. Biochemistry, 54, 4075-4082. PubMed id: 26062720 DOI: 10.1021/acs.biochem.5b00431

Date:

22-Mar-15 Release date: 24-Jun-15

Protein chain

O34453  (NOSO_BACSU) -  Nitric oxide synthase oxygenase from Bacillus subtilis (strain 168)

Seq: 363 a.a.

Struc: 362 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.14.14.47 - nitric-oxide synthase (flavodoxin).
• Reaction: 3 reduced [flavodoxin] + 2 L-arginine + 4 O2 = 3 oxidized [flavodoxin] + 2 L-citrulline + 2 nitric oxide + 4 H2O + 5 H⁺
• Cofactor: 5,6,7,8-tetrahydrobiopterin; Ferriheme b

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

reference

DOI no: 10.1021/acs.biochem.5b00431

Biochemistry 54:4075-4082 (2015)

PubMed id: 26062720

Inhibitor Bound Crystal Structures of Bacterial Nitric Oxide Synthase.

J.K.Holden, D.Dejam, M.C.Lewis, H.Huang, S.Kang, Q.Jing, F.Xue, R.B.Silverman, T.L.Poulos.

ABSTRACT

Nitric oxide generated by bacterial nitric oxide synthase (NOS) increases the susceptibility of Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. Not surprisingly, NOS inhibitors also improve the effectiveness of antimicrobials. Development of potent and selective bacterial NOS inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian NOS isoforms. To exploit bacterial NOS for the development of new therapeutics, recognition of alternative NOS surfaces and pharmacophores suitable for drug binding is required. Here, we report on a wide number of inhibitor-bound bacterial NOS crystal structures to identify several compounds that interact with surfaces unique to the bacterial NOS. Although binding studies indicate that these inhibitors weakly interact with the NOS active site, many of the inhibitors reported here provide a revised structural framework for the development of new antimicrobials that target bacterial NOS. In addition, mutagenesis studies reveal several key residues that unlock access to bacterial NOS surfaces that could provide the selectivity required to develop potent bacterial NOS inhibitors.