title: Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.
abstract: BACKGROUND
  Cercarial elastase is the major invasive larval protease in Schistosoma mansoni, a parasitic blood fluke, and is essential for host skin invasion. Genome sequence analysis reveals a greatly expanded family of cercarial elastase gene isoforms in Schistosoma mansoni. This expansion appears to be unique to S. mansoni, and it is unknown whether gene duplication has led to divergent protease function.
  
  
  METHODS
  Profiling of transcript and protein expression patterns reveals that cercarial elastase isoforms are similarly expressed throughout the S. mansoni life cycle. Computational modeling predicts key differences in the substrate-binding pockets of various cercarial elastase isoforms, suggesting a diversification of substrate preferences compared with the ancestral gene of the family. In addition, active site labeling of SmCE reveals that it is activated prior to exit of the parasite from its intermediate snail host.
  
  
  CONCLUSIONS
  The expansion of the cercarial gene family in S. mansoni is likely to be an example of gene dosage. In addition to its critical role in human skin penetration, data presented here suggests a novel role for the protease in egress from the intermediate snail host. This study demonstrates how enzyme activity-based analysis complements genomic and proteomic studies, and is key in elucidating proteolytic function.
authors.affiliation: Tetrad Graduate Program, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Ingram
authors.forename: Salma B
authors.initials: SB
authors.lastname: Rafi
authors.forename: A Alegra
authors.initials: AA
authors.lastname: Eroy-Reveles
authors.forename: Manisha
authors.initials: M
authors.lastname: Ray
authors.forename: Laura
authors.initials: L
authors.lastname: Lambeth
authors.forename: Ivy
authors.initials: I
authors.lastname: Hsieh
authors.forename: Debbie
authors.initials: D
authors.lastname: Ruelas
authors.forename: K C
authors.initials: KC
authors.lastname: Lim
authors.forename: Judy
authors.initials: J
authors.lastname: Sakanari
authors.forename: Charles S
authors.initials: CS
authors.lastname: Craik
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jacobson
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D058487:Cercaria / Q000201:enzymology / Q000235:genetics; D006224:Cricetinae; D020869:Gene Expression Profiling; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012908:Snails
chemical_list: D010196:Pancreatic Elastase