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PDBsum entry 4jsj
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Oxidoreductase/oxidoreductase inhibitor
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PDB id
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4jsj
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PDB id:
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| Name: |
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Oxidoreductase/oxidoreductase inhibitor
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Title:
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Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(((5-(((3-fluorophenethyl)amino)methyl)pyridin-3-yl)oxy) methyl)-4-methylpyridin-2-amine
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Structure:
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Nitric oxide synthase, brain. Chain: a, b. Fragment: heme domain (unp residues 297-718). Synonym: bnos, constitutive nos, nc-nos, nos type i, neuronal nos, n- nos, nnos, peptidyl-cysteine s-nitrosylase nos1. Engineered: yes
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Source:
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Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: nos1, bnos. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.92Å
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R-factor:
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0.195
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R-free:
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0.225
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Authors:
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H.Li,T.L.Poulos
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Key ref:
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Q.Jing
et al.
(2013).
In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.
Bioorg Med Chem Lett,
21,
5323-5331.
PubMed id:
DOI:
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Date:
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22-Mar-13
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Release date:
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07-Aug-13
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PROCHECK
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Headers
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References
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P29476
(NOS1_RAT) -
Nitric oxide synthase 1 from Rattus norvegicus
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Seq:
Struc:
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1429 a.a.
407 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.1.14.13.39
- nitric-oxide synthase (NADPH).
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Reaction:
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2 L-arginine + 3 NADPH + 4 O2 + H+ = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
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2
×
L-arginine
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+
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3
×
NADPH
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+
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4
×
O2
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+
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H(+)
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=
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2
×
L-citrulline
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+
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2
×
nitric oxide
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+
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3
×
NADP(+)
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+
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4
×
H2O
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
21:5323-5331
(2013)
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PubMed id:
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In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.
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Q.Jing,
H.Li,
J.Fang,
L.J.Roman,
P.Martásek,
T.L.Poulos,
R.B.Silverman.
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ABSTRACT
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In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are
produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important
to develop inhibitors selective for nNOS that do not interfere with other NOS
isoforms, especially endothelial NOS (eNOS), which is critical for proper
functioning of the cardiovascular system. While we have been successful in
developing potent and isoform-selective inhibitors, such as lead compounds 1 and
2, the ease of synthesis and bioavailability have been problematic. Here we
describe a new series of compounds including crystal structures of NOS-inhibitor
complexes that integrate the advantages of easy synthesis and good biological
properties compared to the lead compounds. These results provide the basis for
additional structure-activity relationship (SAR) studies to guide further
improvement of isozyme selective inhibitors.
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Links
