Year: 2016
Type: article
Abstract: Serine protease inhibitors (serpins) in insects function within development, wound healing and immunity. The genome of the African malaria vector, Anopheles gambiae, encodes 23 distinct serpin proteins, several of which are implicated in disease-relevant physiological responses. A. gambiae serpin 18 (SRPN18) was previously categorized as non-inhibitory based on the sequence of its reactive-center loop (RCL), a region responsible for targeting and initiating protease inhibition. The crystal structure of A. gambiae SRPN18 was determined to a resolution of 1.45 Å, including nearly the entire RCL in one of the two molecules in the asymmetric unit. The structure reveals that the SRPN18 RCL is extremely short and constricted, a feature associated with noncanonical inhibitors or non-inhibitory serpin superfamily members. Furthermore, the SRPN18 RCL does not contain a suitable protease target site and contains a large number of prolines. The SRPN18 structure therefore reveals a unique RCL architecture among the highly conserved serpin fold.
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Energy, Industrial Macromolecular Crystallography Association Collaborative Access Team, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Basic Energy Sciences
Awards: G102163711, G1286251239, G1505794299, Protein Structure and Function, G2101401529, G2287611682, G262962599, G409777406, G426311843, G4269241360, G498139845, G5106849484, G5387317844, G5607048534, G5910536577, G679228813, G6848031779, G6918803902, G7368700025, G7583137537, G8546385581, Protein Structure and Function, G8854876071, G9000188091, G9000257712, G969889393, G993149817
OpenAlex ID: W2554870140