Mechanism of the CO-sensing heme protein CooA: New insights from the truncated heme domain and UVRR spectroscopy

Ibrahim, Mohammed; Kuchinskas, Michael; Youn, Hwan; Kerby, Robert L.; Roberts, Gary P.; Poulos, T.L.; Spiro, Thomas G.

doi:10.1016/j.jinorgbio.2007.07.010

Cited by 16 publications

(17 citation statements)

References 28 publications

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“…Therefore, it is suggested that DNA binding or truncation of the DNA-binding domain leads to a reduction in the volume of the distal pocket. This view agrees with UV resonance Raman results that monitor the vibrational modes associated with Trp-110 in the C-helix (13,14). Comparison of the Trp-110 bands of the inactive ferrous RrCooA with those of RrCooACO shows that these bands are enhanced upon CO binding (13,14).…”

Section: Discussionsupporting

confidence: 86%

“…1C). In this structure, one of the monomers is without its heme, but the other one contains a CO-bound heme and shows heme sliding and C-helix displacement similar to those predicted by resonance Raman and UV resonance Raman studies (11)(12)(13)(14). The structure also shows an unexpected movement of the N-terminal region, displaced by CO, so that it is repositioned between the heme and the DNA-binding domains.…”

supporting

confidence: 65%

“…Large conformational changes are needed to expose and position the two recognition helices in the correct orientation required for DNA binding (10). Resonance Raman investigations of RrCooA and several key mutants have led to a plausible mechanistic model explaining various aspects of CooA activation by CO binding (11)(12)(13)(14). This model suggests that, upon CO binding, the conformational changes that rearrange the DNA-binding domain into the proper orientation for specific DNA binding are triggered by the sliding of the heme into an adjacent cavity along with a displacement of the C-helix toward the opposite heme.…”

mentioning

confidence: 99%

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Effect of DNA Binding on Geminate CO Recombination Kinetics in CO-sensing Transcription Factor CooA

Benabbas

Karunakaran

Youn

et al. 2012

Journal of Biological Chemistry

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Background: CooA proteins are CO-sensing transcription factors. Results: DNA binding to CooA-CO speeds up geminate rebinding of CO. Conclusion: DNA binding reduces heme heterogeneity and CO rebinding barrier. This along with distal pocket trapping maintains the "on" state long enough for transcription to take place. Significance: This work provides a deeper understanding of the allosteric transition in CooA proteins.

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Section: Discussionsupporting

confidence: 86%

supporting

confidence: 65%

mentioning

confidence: 99%

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Effect of DNA Binding on Geminate CO Recombination Kinetics in CO-sensing Transcription Factor CooA

Benabbas

Karunakaran

Youn

et al. 2012

Journal of Biological Chemistry

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“…S1). CooA resembles Escherichia coli CRP in structure, but reorientation of CooA DNA-binding domains is needed to produce a transcriptionally active state (61). CO binding may accompany a shift in heme position to a hydrophobic cavity and movement of the C-helix of CooA toward the opposite heme to restructure the CO-binding pocket.…”

Section: Cooamentioning

confidence: 99%

“…CO binding may accompany a shift in heme position to a hydrophobic cavity and movement of the C-helix of CooA toward the opposite heme to restructure the CO-binding pocket. This switch reorganizes a hinge between the C-and D-helices to enable DNA-binding domains to interact with DNA (61 2 ] ranges in which it triggers target gene transcription (68). The five-coordinate (deoxy) FixL is "active" and directs induction of genes encoding high O 2 affinity terminal oxidases for microaerobic respiration (the likely main role of FixL in non-N 2 -fixing bacteria/archaea) and for nitrogenase subunits (S. meliloti) or denitrification enzymes (B. japonicum) (67).…”

Section: Cooamentioning

confidence: 99%

Heme Sensor Proteins

Girvan

Munro

2013

Journal of Biological Chemistry

128

116

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Heme is a prosthetic group best known for roles in oxygen transport, oxidative catalysis, and respiratory electron transport. Recent years have seen the roles of heme extended to sensors of gases such as O 2 and NO and cell redox state, and as mediators of cellular responses to changes in intracellular levels of these gases. The importance of heme is further evident from identification of proteins that bind heme reversibly, using it as a signal, e.g. to regulate gene expression in circadian rhythm pathways and control heme synthesis itself. In this minireview, we explore the current knowledge of the diverse roles of heme sensor proteins. Heme-responsive Proteins: Defining FeaturesHeme homeostasis is crucial. Free heme at Ͼ1 M is cytotoxic, mainly by producing reactive oxygen species. Iron intake accounts for only a small proportion of mammalian requirements, so iron recycling (particularly from heme) is critical (1). Tight regulation of heme synthesis/breakdown is needed. Heme regulates its own fate and controls several other biological processes. Heme-responsive proteins elicit cellular responses by binding/debinding heme or via changes in heme ligation (e.g. by gases) or redox state. They can be divided into two classes: nuclear receptor (NR) 2 hemoproteins and heme sensors with no NR function. Each heme-responsive protein has a heme regulatory motif (HRM), usually containing a CP motif (2). The Cys residue of the CP motif is an axial heme ligand. No other residues are conserved across the protein class. The wider relevance of the CP motif is unclear because other hemoproteins (e.g. prostaglandin E 2 synthase, chloroperoxidase, and some cytochromes P450) also have a CP motif. The properties of members of the two main classes are described below. NR HemoproteinsSeveral heme-binding proteins occur in the NR superfamily, which is the largest transcription factor superfamily (summarized in Table 1). NRs bind specific DNA motifs in response to small molecule signaling. They generally share conserved domain architecture, with a DNA-binding region containing two zinc fingers, a ligand-binding domain, and activation domains (3). Usually, ligand binding induces conformational changes that dissociate partner proteins, allowing DNA binding and/or changes to dimerization status or cellular localization that enable the protein to elicit a response. A subfamily of NRs binds heme at their ligand-binding domain and so act as heme sensors, as discussed below. Circadian Rhythm Heme SensorsCircadian rhythms are regulated by feedback loops at transcriptional/translational levels. Heme is critical in this process (4). In vertebrates, the expression of several day/night cycle genes, as well as Rev-erb␣, is controlled by binding a heterodimer of Clock (or NPAS2 (neuronal PAS domain protein 2)) and Bmal1 to their 5Ј-UTR, thus switching on transcription. Expression of Bmal1 and NPAS2/Clock is repressed in turn by binding of Rev-erb␣ to a homodimeric partner (5). Rev-erb␣ and homologs (Rev-erb␤ and E75, with the latter involved in inse...

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Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins

et al. 2011

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The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins.

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Mechanism of the CO-sensing heme protein CooA: New insights from the truncated heme domain and UVRR spectroscopy

Cited by 16 publications

References 28 publications

Effect of DNA Binding on Geminate CO Recombination Kinetics in CO-sensing Transcription Factor CooA

Effect of DNA Binding on Geminate CO Recombination Kinetics in CO-sensing Transcription Factor CooA

Heme Sensor Proteins

Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins

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