Structural and Functional Enrichment Analyses for Antimicrobial Peptides

• Published in: International journal of molecular sciences Vol. 21; no. 22; p. 8783
• Main Authors: Lo, Sheng C, Xie, Zhong-Ru, Chang, Kuan Y
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.11.2020; MDPI
• Subjects: Amino Acid Sequence; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antifungal activities; Antifungal activity; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiparasitic agents; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Binding Sites; Cancer; Classification; Enrichment; enrichment analysis; Fungi - drug effects; Fungi - growth & development; Fungicides; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - growth & development; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - growth & development; Humans; Inclination; knottin; Peptides; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Folding; Protein Interaction Domains and Motifs; Proteins; Sandwich structures; Structure-Activity Relationship; Structure-function relationships; two-layer sandwich architecture; structure–function relationships; two-layer sandwich architecture; knottin; antifungal activities; enrichment analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228783

Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here, we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP, and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to the two-layer sandwich structure of CATH, the knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM Cluster 1 even sustained through the AMPs with a low sequence identity. Moreover, another significant mutual enrichment was observed between the third cluster of TM and anti-Gram-positive-bacterial/anti-Gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.