PDBsum entry: 1r35

Oxidoreductase

PDB id: 1r35

Contents

Protein chains

413 a.a. *

Ligands

SO4

HEM ×2

H4B ×2

I58 ×2

Waters ×394

* Residue conservation analysis

PDB id:

1r35

Name:

Oxidoreductase

Title:

Murine inducible nitric oxide synthase oxygenase dimer, tetrahydrobiopterin and 4r-fluoro-n6-ethanimidoyl-l-lysine

Structure:

Nitric oxide synthase, inducible. Chain: a, b. Fragment: oxygenase domain (residues 66-498). Synonym: nos, type ii, inducible nos, inos, macrophage nos, engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: nos2, inosl. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.252 R-free: 0.285

Authors:

H.S.Shieh,A.M.Stevens,W.C.Stallings

Key ref:

E.A.Hallinan et al. (2003). 4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain. Org Biomol Chem, 1, 3527-3534. PubMed id: 14599013 DOI: 10.1039/b307563j

Date:

30-Sep-03 Release date: 05-Oct-04

Protein chains

P29477  (NOS2_MOUSE) -  Nitric oxide synthase, inducible

Seq: 1144 a.a.

Struc: 413 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 = I58) matches with 44.44% similarity) + 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: 10.1039/b307563j

Org Biomol Chem 1:3527-3534 (2003)

PubMed id: 14599013

4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain.

E.A.Hallinan, S.W.Kramer, S.C.Houdek, W.M.Moore, G.M.Jerome, D.P.Spangler, A.M.Stevens, H.S.Shieh, P.T.Manning, B.S.Pitzele.

ABSTRACT

In the literature, the introduction of fluorine into bioactive molecules has been known to enhance the biological activity relative to the parent molecule. Described in this article is the synthesis of 4R-fluoro-L-NIL (12) and 4,4-difluoro-L-NIL (23) as part of our iNOS program. Both 12 and 23 were found to be selective iNOS inhibitors as shown in Table 2 below. Secondarily, methodology to synthesize orthogonally protected 4-fluoro-L-lysine and 4,4-difluoro-L-lysine has been developed.