Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity

Sylvia Lee-Huang, Vladimir Maiorov, Philip L. Huang, Angela Ng, Chul Lee Hee, Young Tae Chang, Neville Kallenbach, Paul L. Huang, Hao Chia Chen

Research output: Contribution to journalArticle

Abstract

We previously reported that lysozyme accounts for anti-HIV activity associated with the β-core fraction of human chorionic gonadotropin [Lee-Huang, S., Huang, P. L., Sun, Y., Kung, H. F., Blithe, D. L. & Chen, H. C. (1999) Proc Natl Acad Sci U S A 96, 2678-81]. To define the structural and sequence requirements for anti-HIV activity, we carried out peptide fragmentation and activity mapping of human lysozyme. We identified two peptides that consist of 18 and 9 amino acids of human lysozyme (HL18 and HL9), corresponding to residues 98-115 and 107-115. HL18 and HL9 are potent inhibitors of HIV-1 infection and replication with EC50S of 50 to 55 nM, comparable to intact lysozyme. Scrambling the sequence or substitution of key arginine or tryptophan residues results in loss of antiviral activity. HL9, with the sequence RAWVAWRNR, is the smallest peptide we identified with full anti-HIV activity. It forms a pocket with its basic residues on the surface of the molecule. HL9 exists as an α-helix in native human lysozyme, in a region of the protein distinct from the muramidase catalytic site. Monte Carlo peptide folding energy minimizing simulation modeling and CD studies indicate that helical propensity does not correlate with antiviral activity. HL9 blocks HIV-1 viral entrance and replication, and modulates gene expression of HIV-infected cells, affecting pathways involved in survival, stress, TGFβ, p53, NFκB, protein kinase C and hedgehog signaling.

Original languageEnglish (US)
Pages (from-to)4648-4655
Number of pages8
JournalBiochemistry
Volume44
Issue number12
DOIs
StatePublished - Mar 29 2005

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity'. Together they form a unique fingerprint.

  • Cite this

    Lee-Huang, S., Maiorov, V., Huang, P. L., Ng, A., Hee, C. L., Chang, Y. T., Kallenbach, N., Huang, P. L., & Chen, H. C. (2005). Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry, 44(12), 4648-4655. https://doi.org/10.1021/bi0477081