1M7Z

Structure of Nitric Oxide Synthase Heme Protein from Bacillus Subtilis with N-Hydroxy-Arginine and Tetrahydrofolate Bound

Summary for 1M7Z

• Entry DOI: 10.2210/pdb1m7z/pdb
• Related: 1DWW 1M7V
• Descriptor: Nitric oxide synthase, PROTOPORPHYRIN IX CONTAINING FE, N-OMEGA-HYDROXY-L-ARGININE, ... (5 entities in total)
• Functional Keywords: oxygenase, tetrahydrofolate, pterin, bacteria, heme, hydroxy arginine, oxidoreductase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 1
• Total formula weight: 43147.17

Authors

Pant, K.,Bilwes, A.M.,Adak, S.,Stuehr, D.J.,Crane, B.R. (deposition date: 2002-07-23, release date: 2002-10-30, Last modification date: 2024-02-14)

Primary citation

Pant, K.,Bilwes, A.M.,Adak, S.,Stuehr, D.J.,Crane, B.R.
Structure of a nitric oxide synthase heme protein from Bacillus subtilis.
Biochemistry, 41:11071-11079, 2002

PubMed Abstract: Eukaryotic nitric oxide synthases (NOSs) produce nitric oxide to mediate intercellular signaling and protect against pathogens. Recently, proteins homologous to mammalian NOS oxygenase domains have been found in prokaryotes and one from Bacillus subtilis (bsNOS) has been demonstrated to produce nitric oxide [Adak, S., Aulak, K. S., and Stuehr, D. J. (2002) J. Biol. Chem. 277, 16167-16171]. We present structures of bsNOS complexed with the active cofactor tetrahydrofolate and the substrate L-arginine (L-Arg) or the intermediate N(omega)-hydroxy-L-arginine (NHA) to 1.9 or 2.2 A resolution, respectively. The bsNOS structure is similar to those of the mammalian NOS oxygenase domains (mNOS(ox)) except for the absence of an N-terminal beta-hairpin hook and zinc-binding region that interact with pterin and stabilize the mNOS(ox) dimer. Changes in patterns of residue conservation between bacterial and mammalian NOSs correlate to different binding modes for pterin side chains. Residue conservation on a surface patch surrounding an exposed heme edge indicates a likely interaction site for reductase proteins in all NOSs. The heme pockets of bsNOS and mNOS(ox) recognize L-Arg and NHA similarly, although a change from Val to Ile beside the substrate guanidinium may explain the 10-20-fold slower dissociation of product NO from the bacterial enzyme. Overall, these structures suggest that bsNOS functions naturally to produce nitrogen oxides from L-Arg and NHA in a pterin-dependent manner, but that the regulation and purpose of NO production by NOS may be quite different in B. subtilis than in mammals.

PubMed: 12220171
DOI: 10.1021/bi0263715

Experimental method

X-RAY DIFFRACTION (2.14 Å)