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Influence of pH on ...
Influence of pH on the activity of thrombin-derived antimicrobial peptides
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- Holdbrook, Daniel A. (författare)
- A*Star, Bioinformatics Institute (BII),ASTAR, Bioinforrnat Inst, 30 Biopolis St,07-01 Matrix, Singapore 138671, Singapore
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- Singh, Shalini, 1982- (författare)
- Uppsala universitet,Uppsala University,Institutionen för farmaci
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- Choong, Yeu Khai (författare)
- Nanyang Technological University,Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, 59 Nanyang Dr, Singapore 636921, Singapore
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- Petrlova, Jitka (författare)
- Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Univ, Div Dermatol & Venereol, Dept Clin Sci, SE-22184 Lund, Sweden
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- Malmsten, Martin (författare)
- Uppsala universitet,Uppsala University,University of Copenhagen,Institutionen för farmaci,Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark
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- Bond, Peter J. (författare)
- A*Star, Bioinformatics Institute (BII),National University of Singapore,ASTAR, Bioinforrnat Inst, 30 Biopolis St,07-01 Matrix, Singapore 138671, Singapore;Natl Univ Singapore, Dept Biol Sci, 14 Sci Dr, Singapore 117543, Singapore
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- Verma, Navin Kumar (författare)
- Nanyang Technological University,Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, 59 Nanyang Dr, Singapore 636921, Singapore
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- Schmidtchen, Artur (författare)
- Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Bispebjerg Hospital,Nanyang Technological University,Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, 59 Nanyang Dr, Singapore 636921, Singapore;Lund Univ, Div Dermatol & Venereol, Dept Clin Sci, SE-22184 Lund, Sweden;Bispebjerg Hosp, Wound Healing Ctr, Copenhagen, Denmark
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- Saravanan, Rathi (författare)
- Nanyang Technological University,Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, 59 Nanyang Dr, Singapore 636921, Singapore
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- Engelska.
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1860:11, s. 2374-2384
- Relaterad länk:
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The wound environment is characterized by physiological pH changes. Proteolysis of thrombin by wound-derived proteases, such as neutrophil elastase, generates antimicrobial thrombin-derived C-terminal peptides (TCPs), such as HVF18 (HVFRLKKWIQKVIDQFGE). Presence of such TCPs in human wound fluids in vivo, as well as the occurrence of an evolutionarily conserved His residue in the primary amino acid sequence of TCPs, prompted us to investigate the pH-dependent antibacterial action of HVF18, as well as of the prototypic GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE). We show that protonation of this His residue at pH 5.5 increases the antibacterial activity of both TCPs against Gram-negative Escherichia coli by membrane disruption. Physiological salt level (150 mM NaCl) augments antibacterial activity of GKY25 but diminishes for the shorter HVF18. Replacing His with Leu or Ser in GKY25 abolishes the His protonation-dependent increase in antibacterial activity at pH 5.5, whereas substitution with Lys maintains activity at neutral (pH 7.4) and acidic pH. Interestingly, both TCPs display decreased binding affinities to human CD14 with decreasing pH, suggesting a likely switch in mode-of-action, from anti-inflammatory at neutral pH to antibacterial at acidic pH. Together, the results demonstrate that apart from structural prerequisites such as peptide length, charge, and hydrophobicity, the evolutionarily conserved His residue of TCPs influences their antibacterial effects and reveals a previously unknown aspect of TCPs biological action.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Nyckelord
- Antimicrobial peptides
- Gram-negative bacteria
- Host defense peptides
- Lipopolysaccharide
- pH
- Thrombin
- Antimicrobial peptides
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Holdbrook, Danie ...
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Singh, Shalini, ...
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Choong, Yeu Khai
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Petrlova, Jitka
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Malmsten, Martin
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Bond, Peter J.
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Verma, Navin Kum ...
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Schmidtchen, Art ...
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Saravanan, Rathi
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Lunds universitet
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