PDBsum entry 1m00

Oxidoreductase

PDB id: 1m00

Contents

Protein chains

407 a.a. *

Ligands

ACT ×2

HEM ×2

H4B ×2

BHH ×2

Metals

_ZN

Waters ×498

* Residue conservation analysis

PDB id:

1m00

Name:

Oxidoreductase

Title:

Rat neuronal nos heme domain with n-butyl-n'-hydroxyguanidine bound

Structure:

Nitric-oxide synthase. Chain: a, b. Fragment: heme domain. Synonym: nos, type i, neuronal nos, n-nos, nnos, constitutive nos, nc-nos, bnos. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: brain. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.05Å R-factor: 0.229 R-free: 0.270

Authors:

H.Li,H.Shimizu,M.Flinspach,J.Jamal,W.Yang,M.Xian,T.Cai,E.Z.Wen,Q.Jia, P.G.Wang,T.L.Poulos

Key ref:

H.Li et al. (2002). The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis. Biochemistry, 41, 13868-13875. PubMed id: 12437343 DOI: 10.1021/bi020417c

Date:

11-Jun-02 Release date: 27-Nov-02

Protein chains

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

Seq: 1429 a.a.

Struc: 407 a.a.

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 = BHH) matches with 61.54% 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: 10.1021/bi020417c

Biochemistry 41:13868-13875 (2002)

PubMed id: 12437343

The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis.

H.Li, H.Shimizu, M.Flinspach, J.Jamal, W.Yang, M.Xian, T.Cai, E.Z.Wen, Q.Jia, P.G.Wang, T.L.Poulos.

ABSTRACT

A series of N-alkyl-N'-hydroxyguanidine compounds have recently been characterized as non-amino acid substrates for all three nitric oxide synthase (NOS) isoforms which mimic NO formation from N(omega)-hydroxy-L-arginine. Crystal structures of the nNOS heme domain complexed with either N-isopropyl-N'-hydroxyguanidine or N-butyl-N'-hydroxyguanidine reveal two different binding modes in the substrate binding pocket. The binding mode of the latter is consistent with that observed for the substrate N(omega)-hydroxy-L-arginine bound in the nNOS active site. However, the former binds to nNOS in an unexpected fashion, thus providing new insights into the mechanism on how the hydroxyguanidine moiety leads to NO formation. Structural features of substrate binding support the view that the OH-substituted guanidine nitrogen, instead of the hydroxyl oxygen, is the source of hydrogen supplied to the active ferric-superoxy species for the second step of the NOS catalytic reaction.