A structural and dynamic investigation of the inhibition of catalase by nitric oxide

Marco Candelaresi, Andrea Gumiero, Katrin Adamczyk, Kirsty Robb, César Bellota-Antón, Vartul Sangal, John Munnoch, Gregory M Greetham, Michael Towrie, Paul A Hoskisson, Anthony W Parker, Nicholas P Tucker, Martin A Walsh, Neil T Hunt

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Determining the chemical and structural modifications occurring within a protein during fundamental processes such as ligand or substrate binding is essential to building up a complete picture of biological function. Currently, significant unanswered questions relate to the way in which protein structural dynamics fit within the structure-function relationship and to the functional role, if any, of bound water molecules in the active site. Addressing these questions requires a multidisciplinary approach and complementary experimental techniques that, in combination, enhance our understanding of the complexities of protein chemistry. We exemplify this philosophy by applying both physical and biological approaches to investigate the active site chemistry that contributes to the inhibition of the Corynebacterium glutamicum catalase enzyme by nitric oxide. Ultrafast two-dimensional infrared spectroscopy (2D-IR) experiments exploit the NO ligand as a local probe of the active site molecular environment and shows that catalase displays a dynamically-restricted, 'tight,' structure. X-ray crystallography studies of C. glutamicum catalase confirm the presence of a conserved chain of hydrogen-bonded bound water molecules that link the NO ligand and the protein scaffold. This combination of bound water and restricted dynamics stands in stark contrast to other haem proteins, such as myoglobin, that exhibit ligand transport functionality despite the presence of a similar distal architecture in close proximity to the ligand. We conclude not only that the bound water molecules in the catalase active site play an important role in molecular recognition of NO but also may be part of the mechanistic operation of this important enzyme.
Original languageEnglish
Pages (from-to)7778-7788
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number44
Early online date7 Oct 2013
DOIs
Publication statusPublished - 30 Oct 2013

Fingerprint

catalase
nitric oxide
Catalase
Nitric Oxide
Ligands
proteins
Catalytic Domain
ligands
Corynebacterium glutamicum
Water
Proteins
water
Molecules
enzymes
molecules
Molecular recognition
myoglobin
dynamic structural analysis
Myoglobin
X ray crystallography

Keywords

  • catalase
  • nitric oxide
  • protein modifications
  • corynebacterium glutamicum

Cite this

Candelaresi, M., Gumiero, A., Adamczyk, K., Robb, K., Bellota-Antón, C., Sangal, V., ... Hunt, N. T. (2013). A structural and dynamic investigation of the inhibition of catalase by nitric oxide. Organic and Biomolecular Chemistry, 11(44), 7778-7788. https://doi.org/10.1039/c3ob41977k
Candelaresi, Marco ; Gumiero, Andrea ; Adamczyk, Katrin ; Robb, Kirsty ; Bellota-Antón, César ; Sangal, Vartul ; Munnoch, John ; Greetham, Gregory M ; Towrie, Michael ; Hoskisson, Paul A ; Parker, Anthony W ; Tucker, Nicholas P ; Walsh, Martin A ; Hunt, Neil T. / A structural and dynamic investigation of the inhibition of catalase by nitric oxide. In: Organic and Biomolecular Chemistry. 2013 ; Vol. 11, No. 44. pp. 7778-7788.
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Candelaresi, M, Gumiero, A, Adamczyk, K, Robb, K, Bellota-Antón, C, Sangal, V, Munnoch, J, Greetham, GM, Towrie, M, Hoskisson, PA, Parker, AW, Tucker, NP, Walsh, MA & Hunt, NT 2013, 'A structural and dynamic investigation of the inhibition of catalase by nitric oxide', Organic and Biomolecular Chemistry, vol. 11, no. 44, pp. 7778-7788. https://doi.org/10.1039/c3ob41977k

A structural and dynamic investigation of the inhibition of catalase by nitric oxide. / Candelaresi, Marco; Gumiero, Andrea; Adamczyk, Katrin; Robb, Kirsty; Bellota-Antón, César; Sangal, Vartul; Munnoch, John; Greetham, Gregory M; Towrie, Michael; Hoskisson, Paul A; Parker, Anthony W; Tucker, Nicholas P; Walsh, Martin A; Hunt, Neil T.

In: Organic and Biomolecular Chemistry, Vol. 11, No. 44, 30.10.2013, p. 7778-7788.

Research output: Contribution to journalArticle

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T1 - A structural and dynamic investigation of the inhibition of catalase by nitric oxide

AU - Candelaresi, Marco

AU - Gumiero, Andrea

AU - Adamczyk, Katrin

AU - Robb, Kirsty

AU - Bellota-Antón, César

AU - Sangal, Vartul

AU - Munnoch, John

AU - Greetham, Gregory M

AU - Towrie, Michael

AU - Hoskisson, Paul A

AU - Parker, Anthony W

AU - Tucker, Nicholas P

AU - Walsh, Martin A

AU - Hunt, Neil T

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N2 - Determining the chemical and structural modifications occurring within a protein during fundamental processes such as ligand or substrate binding is essential to building up a complete picture of biological function. Currently, significant unanswered questions relate to the way in which protein structural dynamics fit within the structure-function relationship and to the functional role, if any, of bound water molecules in the active site. Addressing these questions requires a multidisciplinary approach and complementary experimental techniques that, in combination, enhance our understanding of the complexities of protein chemistry. We exemplify this philosophy by applying both physical and biological approaches to investigate the active site chemistry that contributes to the inhibition of the Corynebacterium glutamicum catalase enzyme by nitric oxide. Ultrafast two-dimensional infrared spectroscopy (2D-IR) experiments exploit the NO ligand as a local probe of the active site molecular environment and shows that catalase displays a dynamically-restricted, 'tight,' structure. X-ray crystallography studies of C. glutamicum catalase confirm the presence of a conserved chain of hydrogen-bonded bound water molecules that link the NO ligand and the protein scaffold. This combination of bound water and restricted dynamics stands in stark contrast to other haem proteins, such as myoglobin, that exhibit ligand transport functionality despite the presence of a similar distal architecture in close proximity to the ligand. We conclude not only that the bound water molecules in the catalase active site play an important role in molecular recognition of NO but also may be part of the mechanistic operation of this important enzyme.

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