Abstract
Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6-2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.
Highlights
Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects
While the lipase serves in the nutrition of C. acnes and maintenance of healthy skin, excessive products are known as major factors of inflammation
The degree of lipase activity was elevated in type IA C. acnes [16, 28, 29]
Summary
Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. The pathogenicity is thought to be due to substances generated by C. acnes, such as free fatty acids, extracellular enzymes, or virulence factors [6, 7] It is one of the most common bacteria on human skin that metabolizes sebum and releases fatty acids by secreting lipases in healthy skin. In this process, skin acidity is maintained and this functions as a natural barrier from harmful pathogens, providing innate skin immunity [8]. To understand different roles depending on C. acnes types, genetic studies based on sequence data are being conducted [18, 19]
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