title: 1.45 Å resolution structure of SRPN18 from the malaria vector Anopheles gambiae.
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.
authors.affiliation: Division of Biology, Kansas State University, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Meekins
authors.affiliation: Division of Biology, Kansas State University, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: IMCA-CAT, Hauptman-Woodward Medical Research Institute, Argonne National Laboratory, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Battaile
authors.affiliation: Protein Structure Laboratory, Del Shankel Structural Biology Center, University of Kansas, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Lovell
authors.affiliation: Division of Biology, Kansas State University, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Michel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D011994:Recombinant Proteins; D015843:Serpins
keywords: Anopheles gambiae; enzyme inhibitors; insect immunity; malaria vector; mosquito; serine proteases; serpins