yCP beta5-A49S mutant in complex with the epoxyketone inhibitor ONX 0914

Bortezomib-Resistant Mutant Proteasomes: Structural and Biochemical Evaluation with Carfilzomib and ONX 0914.

LN2 COOLED FIXED-EXIT. SI(111) MONOCHROMATOR

Probable proteasome subunit alpha type-7

MTDRYSFSLTTFSPSGKLGQIDYALTAVKQGVTSLGIKATNGVVIATEKKSSSPLAMSETLSKVSLLTPDIGAVYSGMGP
DYRVLVDKSRKVAHTSYKRIYGEYPPTKLLVSEVAKIMQEATQSGGVRPFGVSLLIAGHDEFNGFSLYQVDPSGSYFPWK
ATAIGKGSVAAKTFLEKRWNDELELEDAIHIALLTLKESVEGEFNGDTIELAIIGDENPDLLGYTGIPTDKGPRFRKLTS
QEINDRLEAL

MGSRRYDSRTTIFSPEGRLYQVEYALESISHAGTAIGIMASDGIVLAAERKVTSTLLEQDTSTEKLYKLNDKIAVAVAGL
TADAEILINTARIHAQNYLKTYNEDIPVEILVRRLSDIKQGYTQHGGLRPFGVSFIYAGYDDRYGYQLYTSNPSGNYTGW
KAISVGANTSAAQTLLQMDYKDDMKVDDAIELALKTLSKTTDSSALTYDRLEFATIRKGANDGEVYQKIFKPQEIKDILV
KTGITKKDEDEEADEDMK

MSGYDRALSIFSPDGHIFQVEYALEAVKRGTCAVGVKGKNCVVLGCERRSTLKLQDTRITPSKVSKIDSHVVLSFSGLNA
DSRILIEKARVEAQSHRLTLEDPVTVEYLTRYVAGVQQRYTQSGGVRPFGVSTLIAGFDPRDDEPKLYQTEPSGIYSSWS
AQTIGRNSKTVREFLEKNYDRKEPPATVEECVKLTVRSLLEVVQTGAKNIEITVVKPDSDIVALSSEEINQYVTQIEQEK
QEQQEQDKKKKSNH

MFLTRSEYDRGVSTFSPEGRLFQVEYSLEAIKLGSTAIGIATKEGVVLGVEKRATSPLLESDSIEKIVEIDRHIGCAMSG
LTADARSMIEHARTAAVTHNLYYDEDINVESLTQSVCDLALRFGEGASGEERLMSRPFGVALLIAGHDADDGYQLFHAEP
SGTFYRYNAKAIGSGSEGAQAELLNEWHSSLTLKEAELLVLKILKQVMEEKLDENNAQLSCITKQDGFKIYDNEKTAELI
KELKEKEAAESPEEADVEMS

MFRNNYDGDTVTFSPTGRLFQVEYALEAIKQGSVTVGLRSNTHAVLVALKRNADELSSYQKKIIKCDEHMGLSLAGLAPD
ARVLSNYLRQQCNYSSLVFNRKLAVERAGHLLCDKAQKNTQSYGGRPYGVGLLIIGYDKSGAHLLEFQPSGNVTELYGTA
IGARSQGAKTYLERTLDTFIKIDGNPDELIKAGVEAISQSLRDESLTVDNLSIAIVGKDTPFTIYDGEAVAKYI

MTSIGTGYDLSNSVFSPDGRNFQVEYAVKAVENGTTSIGIKCNDGVVFAVEKLITSKLLVPQKNVKIQVVDRHIGCVYSG
LIPDGRHLVNRGREEAASFKKLYKTPIPIPAFADRLGQYVQAHTLYNSVRPFGVSTIFGGVDKNGAHLYMLEPSGSYWGY
KGAATGKGRQSAKAELEKLVDHHPEGLSAREAVKQAAKIIYLAHEDNKEKDFELEISWCSLSETNGLHKFVKGDLLQEAI
DFAQKEINGDDDEDEDDSDNVMSSDDENAPVATNANATTDQEGDIHLE

MSGAAAASAAGYDRHITIFSPEGRLYQVEYAFKATNQTNINSLAVRGKDCTVVISQKKVPDKLLDPTTVSYIFCISRTIG
MVVNGPIPDARNAALRAKAEAAEFRYKYGYDMPCDVLAKRMANLSQIYTQRAYMRPLGVILTFVSVDEELGPSIYKTDPA
GYYVGYKATATGPKQQEITTNLENHFKKSKIDHINEESWEKVVEFAITHMIDALGTEFSKNDLEVGVATKDKFFTLSAEN
IEERLVAIAEQD

TTIVGVKFNNGVVIAADTRSTQGPIVADKNCAKLHRISPKIWCAGAGTAADTEAVTQLIGSNIELHSLYTSREPRVVSAL
QMLKQHLFKYQGHIGAYLIVAGVDPTGSHLFSIHAHGSTDVGYYLSLGSGSLAAMAVLESHWKQDLTKEEAIKLASDAIQ
AGIWNDLGSGSNVDVCVMEIGKDAEYLRNYLTPNVREEKQKSYKFPRGTTAVLKESIVNICDIQEEQVDITA

MSDPSSINGGIVVAMTGKDCVAIACDLRLGSQSLGVSNKFEKIFHYGHVFLGITGLATDVTTLNEMFRYKTNLYKLKEER
AIEPETFTQLVSSSLYERRFGPYFVGPVVAGINSKSGKPFIAGFDLIGCIDEAKDFIVSGTASDQLFGMCESLYEPNLEP
EDLFETISQALLNAADRDALSGWGAVVYIIKKDEVVKRYLKMRQD

MDIILGIRVQDSVILASSKAVTRGISVLKDSDDKTRQLSPHTLMSFAGEAGDTVQFAEYIQANIQLYSIREDYELSPQAV
SSFVRQELAKSIRSRRPYQVNVLIGGYDKKKNKPELYQIDYLGTKVELPYGAHGYSGFYTFSLLDHHYRPDMTTEEGLDL
LKLCVQELEKRMPMDFKGVIVKIVDKDGIRQVDDFQAQ

TTTLAFRFQGGIIVAVDSRATAGNWVASQTVKKVIEINPFLLGTMAGGSADCQFWETWLGSQCRLHELREKERISVAAAS
KILSNLVYQYKGAGLSMGTMICGYTRKEGPTIYYVDSDGTRLKGDIFCVGSGQTFAYGVLDSNYKWDLSVEDALYLGKRS
ILAAAHRDAYSGGSVNLYHVTEDGWIYHGNHDVGELFWKVKEEEGSFNNVIG

QFNPYGDNGGTILGIAGEDFAVLAGDTRNITDYSINSRYEPKVFDCGDNIVMSANGFAADGDALVKRFKNSVKWYHFDHN
DKKLSINSAARNIQHLLYGKRFFPYYVHTIIAGLDEDGKGAVYSFDPVGSYEREQCRAGGAAASLIMPFLDNQVNFKNQY
EPGTNGKVKKPLKYLSVEEVIKLVRDSFTSATERHIQVGDGLEILIVTKDGVRKEFYELKRD

TQIANAGASPMVNTQQPIVTGTSVISMKYDNGVIIAADNLGSYGSLLRFNGVERLIPVGDNTVVGISGDISDMQHIERLL
KDLVTENAYDNPLADAEEALEPSYIFEYLATVMYQRRSKMNPLWNAIIVAGVQSNGDQFLRYVNLLGVTYSSPTLATGFG
AHMANPLLRKVVDRESDIPKTTVQVAEEAIVNAMRVLYYRDARSSRNFSLAIIDKNTGLTFKKNLQVENMKWDFAKDIKG
YGTQKI

TSIMAVTFKDGVILGADSRTTTGAYIANRVTDKLTRVHDKIWCCRSGSAADTQAIADIVQYHLELYTSQYGTPSTETAAS
VFKELCYENKDNLTAGIIVAGYDDKNKGEVYTIPLGGSVHKLPYAIAGSGSTFIYGYCDKNFRENMSKEETVDFIKHSLS
QAIKWDGSSGGVIRMVVLTAAGVERLIFYPDEYEQL

20 MM MGAC2, 13% MPD, PH 6.8, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 293K

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Cancer, Proteasome, Bortezomib, Drug Resistance, Binding Analysis, HYDROLASE-HYDROLASE INHIBITOR complex

TTTLAFRFQGGIIVAVDSRATAGNWVASQTVKKVIEINPFLLGTMAGGAADCQFWETWLGSQCRLHELREKERISVAAAS
KILSNLVYQYKGAGLSMGTMICGYTRKEGPTIYYVDSDGTRLKGDIFCVGSGQTFAYGVLDSNYKWDLSVEDALYLGKRS
ILAAAHRDAYSGGSVNLYHVTEDGWIYHGNHDVGELFWKVKEEEGSFNNVIG