|
|
|
|
Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni
|
|
|
|
|
|
|
|
نویسنده
|
ingram j.r. ,rafi s.b. ,eroy-reveles a.a. ,ray m. ,lambeth l. ,hsieh i. ,ruelas d. ,lim k.c. ,sakanari j. ,craik c.s. ,jacobson m.p. ,mckerrow j.h.
|
|
منبع
|
plos neglected tropical diseases - 2012 - دوره : 6 - شماره : 4
|
|
چکیده
|
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. © 2012 ingram et al.
|
|
|
|
|
آدرس
|
tetrad graduate program,university of california san francisco,san francisco,ca,united states,whitehead institute for biomedical research,cambridge,ma, United States, department of pharmaceutical chemistry,university of california san francisco,san francisco,ca, United States, department of pharmaceutical chemistry,university of california san francisco,san francisco,ca,united states,department of chemistry and biochemistry,san francisco state university,san francisco,ca, United States, tetrad graduate program,university of california san francisco,san francisco,ca, United States, department of pharmaceutical chemistry,university of california san francisco,san francisco,ca, United States, department of pathology,university of california san francisco,san francisco,ca, United States, department of pathology,university of california san francisco,san francisco,ca, United States, department of pathology,university of california san francisco,san francisco,ca, United States, sandler center for drug discovery,university of california san francisco,san francisco,ca, United States, department of pharmaceutical chemistry,university of california san francisco,san francisco,ca, United States, department of pharmaceutical chemistry,university of california san francisco,san francisco,ca, United States, department of pathology,university of california san francisco,san francisco,ca,united states,sandler center for drug discovery,university of california san francisco,san francisco,ca, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|