Snake venom phospholipases A(2): a novel tool against bacterial diseases

R P Samy, P Gopalakrishnakone, B G Stiles, K S Girish, S N Swamy, M Hemshekhar, K S Tan, E G Rowan, G Sethi, V T K Chow

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The majority of snake venom phospholipases A(2) (svPLA(2)s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β-sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium- dependent catalytic mechanism. Additionally, svPLA(2)s display an array of biological actions that are either dependent or independent of catalysis. The PLA(2)s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gram-negatives by svPLA(2) requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic- based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA(2)s, which include "fatal depolarization" of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA(2)s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA(2)-derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA(2)s is bactericidal. Thus identification of the bactericidal sites in svPLA(2)s has potential for developing novel antimicrobials.
LanguageEnglish
Pages6150-6162
Number of pages13
JournalCurrent Medicinal Chemistry
Volume19
Issue number36
Publication statusPublished - 2012

Fingerprint

Snake Venoms
Phospholipases A
Membranes
Peptides
Cysteine
Poisons
Normal Distribution
Lipid Bilayers
Catalysis
Disulfides
Phospholipids
Calcium
Amino Acids
Infection
Proteins

Keywords

  • bacterial diseases
  • snake venom
  • phospholipases A(2)

Cite this

Samy, R. P., Gopalakrishnakone, P., Stiles, B. G., Girish, K. S., Swamy, S. N., Hemshekhar, M., ... Chow, V. T. K. (2012). Snake venom phospholipases A(2): a novel tool against bacterial diseases. Current Medicinal Chemistry, 19(36), 6150-6162.
Samy, R P ; Gopalakrishnakone, P ; Stiles, B G ; Girish, K S ; Swamy, S N ; Hemshekhar, M ; Tan, K S ; Rowan, E G ; Sethi, G ; Chow, V T K. / Snake venom phospholipases A(2) : a novel tool against bacterial diseases. In: Current Medicinal Chemistry. 2012 ; Vol. 19, No. 36. pp. 6150-6162.
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Samy, RP, Gopalakrishnakone, P, Stiles, BG, Girish, KS, Swamy, SN, Hemshekhar, M, Tan, KS, Rowan, EG, Sethi, G & Chow, VTK 2012, 'Snake venom phospholipases A(2): a novel tool against bacterial diseases' Current Medicinal Chemistry, vol. 19, no. 36, pp. 6150-6162.

Snake venom phospholipases A(2) : a novel tool against bacterial diseases. / Samy, R P; Gopalakrishnakone, P; Stiles, B G; Girish, K S; Swamy, S N; Hemshekhar, M; Tan, K S; Rowan, E G; Sethi, G; Chow, V T K.

In: Current Medicinal Chemistry, Vol. 19, No. 36, 2012, p. 6150-6162.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Snake venom phospholipases A(2)

T2 - Current Medicinal Chemistry

AU - Samy, R P

AU - Gopalakrishnakone, P

AU - Stiles, B G

AU - Girish, K S

AU - Swamy, S N

AU - Hemshekhar, M

AU - Tan, K S

AU - Rowan, E G

AU - Sethi, G

AU - Chow, V T K

PY - 2012

Y1 - 2012

N2 - The majority of snake venom phospholipases A(2) (svPLA(2)s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β-sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium- dependent catalytic mechanism. Additionally, svPLA(2)s display an array of biological actions that are either dependent or independent of catalysis. The PLA(2)s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gram-negatives by svPLA(2) requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic- based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA(2)s, which include "fatal depolarization" of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA(2)s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA(2)-derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA(2)s is bactericidal. Thus identification of the bactericidal sites in svPLA(2)s has potential for developing novel antimicrobials.

AB - The majority of snake venom phospholipases A(2) (svPLA(2)s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β-sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium- dependent catalytic mechanism. Additionally, svPLA(2)s display an array of biological actions that are either dependent or independent of catalysis. The PLA(2)s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gram-negatives by svPLA(2) requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic- based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA(2)s, which include "fatal depolarization" of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA(2)s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA(2)-derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA(2)s is bactericidal. Thus identification of the bactericidal sites in svPLA(2)s has potential for developing novel antimicrobials.

KW - bacterial diseases

KW - snake venom

KW - phospholipases A(2)

M3 - Article

VL - 19

SP - 6150

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JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

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ER -

Samy RP, Gopalakrishnakone P, Stiles BG, Girish KS, Swamy SN, Hemshekhar M et al. Snake venom phospholipases A(2): a novel tool against bacterial diseases. Current Medicinal Chemistry. 2012;19(36):6150-6162.