PMID- 29461815
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20180515
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Linking)
VI  - 57
IP  - 10
DP  - 2018 Mar 13
TI  - Mechanistic Insights into the Activation of Soluble Guanylate Cyclase by Carbon 
      Monoxide: A Multistep Mechanism Proposed for the BAY 41-2272 Induced Formation of 
      5-Coordinate CO-Heme.
PG  - 1620-1631
LID - 10.1021/acs.biochem.7b01240 [doi]
AB  - Soluble guanylate cyclase (sGC) is a heme-containing enzyme that catalyzes cGMP 
      production upon sensing NO. While the CO adduct, sGC-CO, is much less active, the 
      allosteric regulator BAY 41-2272 stimulates the cGMP productivity to the same 
      extent as that of sGC-NO. The stimulatory effect has been thought to be likely 
      associated with Fe-His bond cleavage leading to 5-coordinate CO-heme, but the 
      detailed mechanism remains unresolved. In this study, we examined the mechanism 
      under the condition including BAY 41-2272, 2'-deoxy-3'-GMP and foscarnet. The 
      addition of these effectors caused the original 6-coordinate CO-heme to convert 
      to an end product that was an equimolar mixture of a 5- and a new 6-coordinate 
      CO-heme, as assessed by IR spectral measurements. The two types of CO-hemes in 
      the end product were further confirmed by CO dissociation kinetics. Stopped-flow 
      measurements under the condition indicated that the ferrous sGC bound CO as two 
      reversible steps, where the primary step was assigned to the full conversion of 
      the ferrous enzyme to the 6-coordinate CO-heme, and subsequently followed by the 
      slower second step leading a partial conversion of the 6-coordinate CO-heme to 
      the 5-coordinate CO-heme. The observed rates for both steps linearly depended on 
      CO concentrations. The unexpected CO dependence of the rates in the second step 
      supports a multistep mechanism, in which the 5-coordinate CO-heme is led by CO 
      release from a putative bis-carbonyl intermediate that is likely provided by the 
      binding of a second CO to the 6-coordinate CO-heme. This mechanism provides a new 
      aspect on the activation of sGC by CO.
FAU - Makino, Ryu
AU  - Makino R
AUID- ORCID: 0000-0002-6890-3797
AD  - Department of Life Science, College of Science , Rikkyo University , 
      Nishi-ikebukuro 3-34-1 , Toshima-ku, Tokyo 171-8501 , Japan.
FAU - Obata, Yuji
AU  - Obata Y
AD  - Department of Life Science, College of Science , Rikkyo University , 
      Nishi-ikebukuro 3-34-1 , Toshima-ku, Tokyo 171-8501 , Japan.
FAU - Tsubaki, Motonari
AU  - Tsubaki M
AD  - Department of Chemistry, Graduate School of Science , Kobe University , Kobe , 
      Hyogo 657-8501 , Japan.
FAU - Iizuka, Tetsutaro
AU  - Iizuka T
AD  - RIKEN Harima Institute/Spring8 , 1-1-1 Kouto , Mikazuki-cho, Sayo-gun , Hyogo 
      679-5148 , Japan.
FAU - Hamajima, Yuki
AU  - Hamajima Y
AD  - Department of Life Science, College of Science , Rikkyo University , 
      Nishi-ikebukuro 3-34-1 , Toshima-ku, Tokyo 171-8501 , Japan.
FAU - Kato-Yamada, Yasuyuki
AU  - Kato-Yamada Y
AD  - Department of Life Science, College of Science , Rikkyo University , 
      Nishi-ikebukuro 3-34-1 , Toshima-ku, Tokyo 171-8501 , Japan.
FAU - Mashima, Keisuke
AU  - Mashima K
AD  - Department of Life Science, College of Science , Rikkyo University , 
      Nishi-ikebukuro 3-34-1 , Toshima-ku, Tokyo 171-8501 , Japan.
FAU - Shiro, Yoshitsugu
AU  - Shiro Y
AD  - Graduate School of Life Science , University of Hyogo , 3-2-1 Kouto , 
      Kamigori-cho, Ako-gun , Hyogo 678-1297 , Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180220
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 
      (3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 42VZT0U6YR (Heme)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
SB  - IM
MH  - Animals
MH  - Carbon Monoxide/*metabolism
MH  - Cattle
MH  - Heme/*metabolism
MH  - Kinetics
MH  - Pyrazoles/*chemistry
MH  - Pyridines/*chemistry
MH  - Soluble Guanylyl Cyclase/*metabolism
MH  - Spectroscopy, Fourier Transform Infrared
MH  - Spectrum Analysis, Raman
EDAT- 2018/02/21 06:00
MHDA- 2018/05/16 06:00
CRDT- 2018/02/21 06:00
PHST- 2018/02/21 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2018/02/21 06:00 [entrez]
AID - 10.1021/acs.biochem.7b01240 [doi]
PST - ppublish
SO  - Biochemistry. 2018 Mar 13;57(10):1620-1631. doi: 10.1021/acs.biochem.7b01240. 
      Epub 2018 Feb 20.