Molecule Information

General Information of the Molecule (ID: Mol01144)
Name
Gamma-glutamylcysteine synthetase (GGCS) ,Plasmodium berghei
Synonyms
Gamma-ECS
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Molecule Type
Protein
Gene Name
ggcs
Sequence
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGE
YCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGT
CHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCE
TDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTG
DFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVD
ECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASF
SCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECA
MANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTC
LCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTP
CLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYM
GAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICM
DGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQ
VNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYR
CTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPN
PCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECP
PGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKN
GGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGS
FCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQ
KKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLG
YTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGG
TCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGER
CEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETFVDVCPQMPCLNGGTCA
VASNMPDGFICRCPPGFSGARCQSSCGQVKCRKGEQCVHTASGPRCFCPSPRDCESGCAS
SPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCD
EACNSHACQWDGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNS
KTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIVVLMPPEQLLQ
DARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAMKKQRMTRRSLPGEQEQEVAG
SKVFLEIDNRQCVQDSDHCFKNTDAAAALLASHAIQGTLSYPLVSVVSESLTPERTQLLY
LLAVAVVIILFIILLGVIMAKRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNL
SVQVSEANLIGTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIR
RTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIIT
DLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAA
DAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSA
LHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITD
HMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMG
KKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSPVDSLESPHTY
VSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALSFSNLHEMQPLAHGASTVLPS
VSQLLSHHHIVSPGSGSAGSLSRLHPVPVPADWMNRMEVNETQYNEMFGMVLAPAEGTHP
GIAPQSRPPEGKHITTPREPLPPMGFLKIGTPLSWEDVQNVKSLIRLYGILQFVHSYKCN
KDRKDEHIMFGDEIEYIIIRNDDKLKEASALLCATDLIDEMMNLESGNDCQYGSHWTPEY
SSFTIEGTPSVPFKFELNSSYFIEHCMKIRRNKLNNVLSGLRGVQAITLPCYPNVLLNNS
LIMAKKINLEKKKKKINKQEIVETSPINYNCIQINKTIHDSESCDENEPRKHISQKNENK
NTSNDIISEDVEENKSTHFVSSDFTQQKYDDLLVPDISMDEVDINNRNDPKNDECVEKED
ECQCDVANETLGIEEEDNIFISTIKENSIFKCELFKPDITSEYSNSCLVTDMVISPHSRY
VTLTKNIRKRRGTKVISFNEIYKDVNTENMDIWKLSLDKNDKRLFKKKLKKTTLDGHLIW
NKSMTNEKKKSEKKNKIKNDETELLDKVIKHSLFSNIDDDEDYIYSYNREFIEEYSKKCK
NPIKNYVYLDAMFFGMSMCCQQITMSFQTINDAKYVYDQLAVIAPLFLAITACTPYLGGF
LTETDARWRVISNSVDCRTEDELSYISKPRYSGISLYISDELPLKKNYYFYNDIDIILNK
NVYDKLIKENVDEYLSRHISSLFVRDPIVVFEGSFSEKDITTIQNIMHEKNENINNSKMW
SEEEMNKIYLSDDFEFLEDYKEKVLSSHQHFENFQSTNWNSVRFKPPPILDNNYLNGPSS
IGWRVEFRTPDIQITDFENASVVALIMTLSKFILKKKLNLYIPMSKLEENLFRSSKRDAI
LKEKFYFRNDINYDTCNNEIEEKSIYDIFFNKNNGILYLCSLYIEEQFEQGLISLSAKNK
INEYIQFIKLRCKGEICTGASFLRKFILNHSAYEQNSYINNQINYDLCKLISDIGKGEIA
PHELLGGFVDPHKERIKNNLRQISKRQYLKSLAYKFISGEDYTQYLLLNEDLKHDKDFFI
QNKHTNYEESDEYIDNNMLEFGKKLYQFSATFQLIPKGSIAQPAGAPQPQSTCPPAVAGP
LPTMYQIPEMARLPSVAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASS
NAAERTPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGGGQRGP
GTHMSEPPHNNMQVYA
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Uniprot ID
Q8WP96_PLABE
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Kingdom: N.A.
Phylum: Apicomplexa
Class: Aconoidasida
Order: Haemosporida
Family: Plasmodiidae
Genus: Plasmodium
Species: Plasmodium berghei
Type(s) of Resistant Mechanism of This Molecule
  DISM: Drug Inactivation by Structure Modification
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
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Glutathione
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Disease Class: Malaria [1]
Sensitive Disease Malaria [ICD-11: 1F45.0]
 Disease Info 
Sensitive Drug Glutathione
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Plasmodium berghei ANkA 2.34 5823
Plasmodium berghei pbggcs-ko 5821
Plasmodium berghei pbggcs-oe 5821
In Vivo Model Swiss albino CD-1 female mice xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 In vivo drug suppressive test assay
Mechanism Description To analyze the role of GSH levels in CQ and ART resistance, we generated transgenic Plasmodium berghei parasites either deficient in or overexpressing the gamma-glutamylcysteine synthetase gene (pbggcs) encoding the rate-limiting enzyme in GSH biosynthesis. These lines produce either lower (pbggcs-ko) or higher (pbggcs-oe) levels of GSH than wild type parasites. Recrudescence assays after the parasites have been exposed to a sub-lethal dose of ART showed that parasites with low levels of GSH are more sensitive to ART tre.
References
Ref 1 Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin. PLoS One. 2015 May 26;10(5):e0128212. doi: 10.1371/journal.pone.0128212. eCollection 2015.

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