8FYG

Crystal structure of Hyaluronate lyase A from Cutibacterium acnes

Summary for 8FYG

• Entry DOI: 10.2210/pdb8fyg/pdb
• Descriptor: Hyaluronate lyase, 1,2-ETHANEDIOL, GLYCEROL, ... (4 entities in total)
• Functional Keywords: polysaccharide lyase, glycosaminoglycan (gag) lyase, hyaluronate lyase, inflammation, lyase
• Biological source: Cutibacterium acnes HL043PA1
• Total number of polymer chains: 2
• Total formula weight: 167670.57

Authors

Katiki, M.,McNally, R.,Chatterjee, A.,Hajam, I.A.,Liu, G.Y.,Murali, R. (deposition date: 2023-01-26, release date: 2023-12-13)

Primary citation

Hajam, I.A.,Katiki, M.,McNally, R.,Lazaro-Diez, M.,Kolar, S.,Chatterjee, A.,Gonzalez, C.,Paulchakrabarti, M.,Choudhury, B.,Caldera, J.R.,Desmond, T.,Tsai, C.M.,Du, X.,Li, H.,Murali, R.,Liu, G.Y.
Functional divergence of a bacterial enzyme promotes healthy or acneic skin.
Nat Commun, 14:8061-8061, 2023

PubMed Abstract: Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.

PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8

Experimental method

X-RAY DIFFRACTION (2.05 Å)