Crystal Structure of Tubulin-Stathmin-TTL-Tubulysin M Complex

(2R,4R)-4-{[(2-{(1R,3R)-1-(acetyloxy)-4-methyl-3-[methyl(N-{[(2S)-1-methylpiperidin-2-yl]carbonyl}-D-isoleucyl)amino]pentyl}-1,3-thiazol-4-yl)carbonyl]amino}-2-methyl-5-phenylpentanoic acid

PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER
ADENOSINE-5'-[BETA, GAMMA-METHYLENE]TRIPHOSPHATE

Structural Insights into the Pharmacophore of Vinca Domain Inhibitors of Microtubules

Alpha-tubulin ubiquitous,Tubulin K-alpha-1,Tubulin alpha-ubiquitous chain

MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGKHVPRAVFVDLEPTVIDEVRT
GTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDLVLDRIRKLADQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVD
YGKKSKLEFSIYPAPQVSTAVVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITA
SLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPANQMVKCDPRHGKYMACCLLYR
GDVVPKDVNAAIATIKTKRSIQFVDWCPTGFKVGINYQPPTVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYA
KRAFVHWYVGEGMEEGEFSEAREDMAALEKDYEEVGVDSVEGEGEEEGEEY

MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNEAAGNKYVPRAILVDLEPGTMDSVRSGP
FGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVVRKESESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYP
DRIMNTFSVVPSPKVSDTVVEPYNATLSVHQLVENTDETYCIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCL
RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDAKNMMAACDPRHGRYLTVAAVFRGR
MSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRGLKMSATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTG
EGMDEMEFTEAESNMNDLVSEYQQYQDATADEQGEFEEEGEEDEA

MADMEVIELNKCTSGQSFEVILKPPSFDGVPEFNASLPRRRDPSLEEIQKKLEAAEERRKYQEAELLKHLAEKREHEREV
IQKAIEENNNFIKMAKEKLAQKMESNKENREAHLAAMLERLQEKDKHAEEVRKNKELKEEASR

MYTFVVRDENSSVYAEVSRLLLATGQWKRLRKDNPRFNLMLGERNRLPFGRLGHEPGLVQLVNYYRGADKLCRKASLVKL
IKTSPELSESCTWFPESYVIYPTNLKTPVAPAQNGIRHLINNTRTDEREVFLAAYNRRREGREGNVWIAKSSAGAKGEGI
LISSEASELLDFIDEQGQVHVIQKYLEKPLLLEPGHRKFDIRSWVLVDHLYNIYLYREGVLRTSSEPYNSANFQDKTCHL
TNHCIQKEYSKNYGRYEEGNEMFFEEFNQYLMDALNTTLENSILLQIKHIIRSCLMCIEPAISTKHLHYQSFQLFGFDFM
VDEELKVWLIEVNGAPACAQKLYAELCQGIVDVAISSVFPLADTGQKTSQPTSIFIKLHHHHHH

6% PEG, 5% glycerol, 0.1M MES, 30 mM CaCl2, 30 mM MgCl2

HYDROGENS HAVE BEEN USED IF PRESENT IN
THE INPUT

DMEVIELNKCTSGQSFEVILKPPSFDGVPEFNASLPRRRDPSLEEIQKKLEAAEERRKYQEAELLKHLAEKREHEREVIQ
KAIEENNNFIKMAKEKLAQKMESNKENREAHLAAMLERLQEKDKHAEEVRKNKELKEEASR

MYTFVVRDENSSVYAEVSRLLLATGQWKRLRKDNPRFNLMLGERNRLPFGRLGHEPGLVQLVNYYRGADKLCRKASLVKL
IKTSPELSESCTWFPESYVIYPTNLKTPVAPAQNGIRHLINNTRTDEREVFLAAYNRRREGREGNVWIAKSSAGAKGEGI
LISSEASELLDFIDEQGQVHVIQKYLEKPLLLEPGHRKFDIRSWVLVDHLYNIYLYREGVLRTSSEPYNSANFQDKTCHL
TNHCIQKEYSKNYGRYEEGNEMFFEEFNQYLMDALNTTLENSILLQIKHIIRSCLMCIEPAISTKHLHYQSFQLFGFDFM
VDEELKVWLIEVNGAPACAQKLYAELCQGIVDVAISSVFPLADTGQKTSQPTSIFIKL