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Article: The role of Thr5 in human neuron growth inhibitory factor

TitleThe role of Thr5 in human neuron growth inhibitory factor
Authors
Issue Date2006
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htm
Citation
Journal Of Biological Inorganic Chemistry, 2006, v. 11 n. 4, p. 476-482 How to Cite?
AbstractGIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits neuron outgrowth in Alzheimer's disease. The conserved Thr5 is one of the main differences between GIF and other members in the MT family. However, natural sheep GIF has an unusual Ala5, casting doubt on the role of common Thr5. We constructed a series of human GIF mutants at site 5, and characterized their biochemical properties by UV spectroscopy, circular dichroism spectroscopy, EDTA reaction, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) reaction, and pH titration. Their inhibitory activity toward neuron survival and neurite extension was also examined. Interestingly, the T5A mutant exhibited distinct metal thiolate activity in the EDTA and DTNB reactions, and also lost its bioactivity. Meanwhile, the T5S mutant had similar biochemical properties and biological activity as wild-type human GIF, indicating the hydroxyl group on the Thr5 was critical to the bioactivity of human GIF. We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation. On the other hand, lack of the hydroxyl group in sheep GIF may be partially compensated by its abnormal structure. © SBIC 2006.
Persistent Identifierhttp://hdl.handle.net/10722/70334
ISSN
2015 Impact Factor: 2.495
2015 SCImago Journal Rankings: 0.882
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCai, Ben_HK
dc.contributor.authorZheng, Qen_HK
dc.contributor.authorTeng, XCen_HK
dc.contributor.authorChen, Den_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorWang, KQen_HK
dc.contributor.authorZhou, GMen_HK
dc.contributor.authorXie, Yen_HK
dc.contributor.authorZhang, MJen_HK
dc.contributor.authorSun, HZen_HK
dc.contributor.authorHuang, ZXen_HK
dc.date.accessioned2010-09-06T06:21:54Z-
dc.date.available2010-09-06T06:21:54Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Biological Inorganic Chemistry, 2006, v. 11 n. 4, p. 476-482en_HK
dc.identifier.issn0949-8257en_HK
dc.identifier.urihttp://hdl.handle.net/10722/70334-
dc.description.abstractGIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits neuron outgrowth in Alzheimer's disease. The conserved Thr5 is one of the main differences between GIF and other members in the MT family. However, natural sheep GIF has an unusual Ala5, casting doubt on the role of common Thr5. We constructed a series of human GIF mutants at site 5, and characterized their biochemical properties by UV spectroscopy, circular dichroism spectroscopy, EDTA reaction, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) reaction, and pH titration. Their inhibitory activity toward neuron survival and neurite extension was also examined. Interestingly, the T5A mutant exhibited distinct metal thiolate activity in the EDTA and DTNB reactions, and also lost its bioactivity. Meanwhile, the T5S mutant had similar biochemical properties and biological activity as wild-type human GIF, indicating the hydroxyl group on the Thr5 was critical to the bioactivity of human GIF. We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation. On the other hand, lack of the hydroxyl group in sheep GIF may be partially compensated by its abnormal structure. © SBIC 2006.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htmen_HK
dc.relation.ispartofJournal of Biological Inorganic Chemistryen_HK
dc.titleThe role of Thr5 in human neuron growth inhibitory factoren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0949-8257&volume=11&spage=476&epage=482&date=2006&atitle=The+role+of+Thr5+in+human+neuron+growth+inhibitory+factoren_HK
dc.identifier.emailSun, HZ:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, HZ=rp00777en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00775-006-0097-6en_HK
dc.identifier.pmid16601975-
dc.identifier.scopuseid_2-s2.0-33745737633en_HK
dc.identifier.hkuros121161en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33745737633&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue4en_HK
dc.identifier.spage476en_HK
dc.identifier.epage482en_HK
dc.identifier.isiWOS:000237340800009-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridCai, B=36484162900en_HK
dc.identifier.scopusauthoridZheng, Q=36887872800en_HK
dc.identifier.scopusauthoridTeng, XC=9842935500en_HK
dc.identifier.scopusauthoridChen, D=7405455814en_HK
dc.identifier.scopusauthoridWang, Y=36078812500en_HK
dc.identifier.scopusauthoridWang, KQ=7501398928en_HK
dc.identifier.scopusauthoridZhou, GM=8449295200en_HK
dc.identifier.scopusauthoridXie, Y=7403958906en_HK
dc.identifier.scopusauthoridZhang, MJ=7601555100en_HK
dc.identifier.scopusauthoridSun, HZ=7404827446en_HK
dc.identifier.scopusauthoridHuang, ZX=7406221847en_HK

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