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Article: The Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability

TitleThe Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2009, v. 4 n. 7 How to Cite?
AbstractReverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln 269-Arg 277) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160 gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. © 2009 Zhang et al.
Persistent Identifierhttp://hdl.handle.net/10722/68199
ISSN
2014 Impact Factor: 3.234
2014 SCImago Journal Rankings: 1.300
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, HJen_HK
dc.contributor.authorWang, YXen_HK
dc.contributor.authorWu, Hen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorWen, YMen_HK
dc.contributor.authorZheng, BJen_HK
dc.date.accessioned2010-09-06T06:02:18Z-
dc.date.available2010-09-06T06:02:18Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos One, 2009, v. 4 n. 7en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68199-
dc.description.abstractReverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln 269-Arg 277) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160 gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. © 2009 Zhang et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAmino Acids - physiology-
dc.subject.meshDNA Primers-
dc.subject.meshHIV Reverse Transcriptase - chemistry - genetics-
dc.subject.meshHIV-1 - enzymology - physiology-
dc.subject.meshMicroscopy, Fluorescence-
dc.titleThe Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stabilityen_HK
dc.typeArticleen_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0006108en_HK
dc.identifier.pmid19578544-
dc.identifier.pmcidPMC2701634-
dc.identifier.scopuseid_2-s2.0-67650252529en_HK
dc.identifier.hkuros168240en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650252529&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue7en_HK
dc.identifier.spagee6108-
dc.identifier.epagee6108-
dc.identifier.isiWOS:000267806300001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, HJ=14124271200en_HK
dc.identifier.scopusauthoridWang, YX=9942220100en_HK
dc.identifier.scopusauthoridWu, H=35216889100en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridWen, YM=7401776949en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK

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