Dynamics of carbon monoxide binding to cystathionine beta-synthase.

The Journal of Biological Chemistry
Mrinalini PuranikThomas G Spiro

Abstract

Cystathionine beta-synthase (CBS) condenses homocysteine, a toxic metabolite, with serine in a pyridoxal phosphate-dependent reaction. It also contains a heme cofactor to which carbon monoxide (CO) or nitric oxide can bind, resulting in enzyme inhibition. To understand the mechanism of this regulation, we have investigated the equilibria and kinetics of CO binding to the highly active catalytic core of CBS, which is dimeric. CBS exhibits strong anticooperativity in CO binding with successive association constants of 0.24 and 0.02 microm(-1). Stopped flow measurements reveal slow CO association (0.0166 s(-1)) limited by dissociation of the endogenous ligand, Cys-52. Rebinding of CO and of Cys-52 following CO photodissociation were independently monitored via time-resolved resonance Raman spectroscopy. The Cys-52 rebinding rate, 4000 s(-1), is essentially unchanged between pH 7.6 and 10.5, indicating that the pK(a) of Cys-52 is shifted below pH 7.6. This effect is attributed to the nearby Arg-266 residue, which is proposed to form a salt bridge with the dissociated Cys-52, thereby inhibiting its protonation and slowing rebinding to the Fe. This salt bridge suggests a pathway for enzyme inactivation upon CO binding, because Arg-26...Continue Reading

References

Sep 17, 1998·The Journal of Biological Chemistry·S TaokaR Banerjee
May 16, 2001·Biochemistry·J T TrentM S Hargrove
Apr 11, 2003·Biochimica Et Biophysica Acta·Markus MeierPeter Burkhard
Mar 3, 2004·The Journal of Biological Chemistry·Mrinalini PuranikThomas G Spiro
Apr 17, 2004·The Journal of Biological Chemistry·Edith Wilson Miles, Jan P Kraus
Nov 17, 2004·Biochemistry·Samuel PazicniJudith N Burstyn
Dec 8, 2004·Archives of Biochemistry and Biophysics·Ruma Banerjee, Cheng-Gang Zou

❮ Previous
Next ❯

Citations

Feb 9, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Scott Vandiver, Solomon H Snyder
Sep 11, 2012·Biochemistry·Luciana HannibalDennis J Stuehr
Nov 15, 2007·Inorganic Chemistry·Thomas G Spiro
Sep 3, 2009·Journal of the American Chemical Society·Colin L WeeksThomas G Spiro
Feb 17, 2010·The Journal of Physical Chemistry. B·Venugopal KarunakaranPaul M Champion
Oct 20, 2007·Nature Reviews. Drug Discovery·Csaba Szabó
May 31, 2007·Natural Product Reports·Sangita SinghRuma Banerjee
Nov 6, 2010·Antioxidants & Redox Signaling·Ruth PietriJuan López-Garriga
Feb 7, 2012·Antioxidants & Redox Signaling·Yi-Hong LiuJin-Song Bian
Feb 8, 2011·Journal of Clinical Biochemistry and Nutrition·Takehiro YamamotoMakoto Suematsu
Apr 23, 2013·Antioxidants & Redox Signaling·Omer Kabil, Ruma Banerjee
Apr 16, 2014·Antioxidants & Redox Signaling·Mark R HellmichCsaba Szabo
Jul 11, 2012·FEMS Microbiology Letters·Ana Filipa N TavaresLígia M Saraiva
Jul 9, 2016·Nitric Oxide : Biology and Chemistry·Krishna C ChintaAdrie J C Steyn
Apr 27, 2017·Antioxidants & Redox Signaling·Andrea K SteigerMichael D Pluth
Jan 13, 2017·American Journal of Physiology. Cell Physiology·Roberto Motterlini, Roberta Foresti
Nov 20, 2015·The Journal of Biological Chemistry·João B VicenteAlessandro Giuffrè
Dec 4, 2010·Clinical Science·Madhav LavuDavid J Lefer
Jul 2, 2016·The Journal of Biological Chemistry·Omer KabilRuma Banerjee
Mar 7, 2019·Oxidative Medicine and Cellular Longevity·Francesca MalagrinòAlessandro Giuffrè
Sep 1, 2018·ChemPlusChem·Tatiana SobolevaLisa M Berreau
Mar 19, 2014·British Journal of Pharmacology·U Schatzschneider
Feb 13, 2016·The Journal of Biological Chemistry·Sebastián CarballalRuma Banerjee
Feb 12, 2014·The Journal of Biological Chemistry·João B VicenteAlessandro Giuffrè
Aug 29, 2018·Oxidative Medicine and Cellular Longevity·Ya-Dan WenYi-Zhun Zhu
Jul 28, 2018·Oxidative Medicine and Cellular Longevity·Alessandro Giuffrè, João B Vicente
Dec 18, 2020·Frontiers in Cellular and Infection Microbiology·Md Aejazur RahmanAdrie J C Steyn
Nov 20, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Karim ZuhraAlessandro Giuffrè
Mar 17, 2021·Critical Reviews in Biochemistry and Molecular Biology·Roshan Kumar, Ruma Banerjee
Feb 19, 2008·Biochemistry·Sebastián CarballalBeatriz Alvarez
Jul 3, 2021·Current Opinion in Structural Biology·Aaron P LandryRuma Banerjee
Jun 25, 2013·Biochemistry·Sebastián CarballalBeatriz Alvarez
Feb 2, 2021·ACS Omega·Dayana BenchoamBeatriz Alvarez

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.