PMID- 15219987
OWN - NLM
STAT- MEDLINE
DCOM- 20050408
LR  - 20231213
IS  - 0162-0134 (Print)
IS  - 0162-0134 (Linking)
VI  - 98
IP  - 7
DP  - 2004 Jul
TI  - Analysis of the kinetics of CO binding to neuronal nitric oxide synthase by flash 
      photolysis: dual effects of substrates, inhibitors, and tetrahydrobiopterin.
PG  - 1210-6
AB  - The effects of substrates, inhibitors and tetrahydrobiopterin (H4B) on CO 
      rebinding to the isolated heme-bound oxygenase domain (nNOSox) of neuronal nitric 
      oxide synthase were examined by laser flash photolysis. The rate constant of CO 
      recombination with substrate and inhibitor-free nNOSox in the absence of H4B was 
      1.0 x 10(6) M(-1) s(-1). The addition of H4B led to a marked decrease in the rate 
      to 0.59 x 10(6) M(-1) s(-1). Interestingly, the substrates, L-Arg and 
      N-hydroxy-L-Arg (NHA), altered CO binding behavior in that the binding rate was 
      modified to CO concentration-independent, both with and without H4B. In the 
      absence of H4B, agmatine, NG-monomethyl-L-Arg (NMMA) and NG-nitro-L-Arg methyl 
      ester (NAME) decreased the CO concentration-dependent rate constants of rebinding 
      by half (0.43 x 10(6) M(-1) s(-1) for the NMMA-bound complex), whereas 
      N6-(l-iminoethyl)-L-Lys (NIL) and 7-nitro-1H-indazole (7-NI) increased the rate 
      constants by more than 70% (up to 2.1 x 10(6) M(-1) s(-1) for the NIL-bound 
      complex). In the presence of H4B, the binding rate was independent of CO 
      concentration for the agmatine-bound complex. The differential effects of the 
      inhibitors on the CO concentration-dependent rate constants were significantly 
      diminished for the H4B-bound system. Interestingly, these variable effects of 
      inhibitors on the CO binding rate were more pronounced in the absence of H4B. 
      Accordingly, we suggest that H4B significantly influences CO binding by altering 
      the CO access channel, and further reduces the divergent effects of different 
      inhibitors.
FAU - Bengea, Simona
AU  - Bengea S
AD  - Institute of Multidisciplinary Research for Advanced Materials, Tohoku 
      University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
FAU - Araki, Yasuyuki
AU  - Araki Y
FAU - Ito, Osamu
AU  - Ito O
FAU - Igarashi, Jotaro
AU  - Igarashi J
FAU - Sagami, Ikuko
AU  - Sagami I
FAU - Shimizu, Toru
AU  - Shimizu T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Biopterins)
RN  - 42VZT0U6YR (Heme)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, rat)
RN  - EGX657432I (sapropterin)
SB  - IM
MH  - Animals
MH  - Biopterins/*analogs & derivatives/*chemistry
MH  - Carbon Monoxide/*chemistry/metabolism
MH  - Enzyme Inhibitors/*chemistry
MH  - Heme/*chemistry
MH  - Kinetics
MH  - Nerve Tissue Proteins/*chemistry/metabolism
MH  - Nitric Oxide Synthase/*chemistry/metabolism
MH  - Nitric Oxide Synthase Type I
MH  - *Photolysis
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Rats
EDAT- 2004/06/29 05:00
MHDA- 2005/04/09 09:00
CRDT- 2004/06/29 05:00
PHST- 2003/11/18 00:00 [received]
PHST- 2004/04/12 00:00 [revised]
PHST- 2004/04/16 00:00 [accepted]
PHST- 2004/06/29 05:00 [pubmed]
PHST- 2005/04/09 09:00 [medline]
PHST- 2004/06/29 05:00 [entrez]
AID - S016201340400128X [pii]
AID - 10.1016/j.jinorgbio.2004.04.009 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2004 Jul;98(7):1210-6. doi: 10.1016/j.jinorgbio.2004.04.009.