Crystal structure of RabGGTase(DELTA LRR; DELTA IG)in complex with mono-prenylated peptide Ser-Cys(GG)-Ser-Cys derivated from Rab7

Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation

CHIRALITY ERROR AT THE CA CENTER OF HIS A 192

Geranylgeranyl transferase type-2 subunit alpha
PFTA domains, UNP residues 1-237 and 353-441

Geranylgeranyl transferase type-2 subunit beta

Geranylgeranyl transferase type II subunit alpha, Rab geranylgeranyltransferase subunit alpha, Rab geranyl-geranyltransferase subunit alpha, Rab GG transferase alpha, Rab GGTase alpha

Geranylgeranyl transferase type II subunit beta, GGTase-II-beta, Type II protein geranyl-geranyltransferase subunit beta, Rab geranylgeranyltransferase subunit beta, Rab geranyl-geranyltransferase subunit beta, Rab GG transferase beta, Rab GGTase beta

HMHGRLKVKTSEEQAEAKRLEREQKLKLYQSATQAVFQKRQAGELDESVLELTSQILGANPDFATLWNCRREVLQHLETE
KSPEESAALVKAELGFLESCLRVNPKSYGTWHHRCWLLSRLPEPNWARELELCARFLEADERNFHCWDYRRFVAAQAAVA
PAEELAFTDSLITRNFSNYSSWHYRSCLLPQLHPQPDSGPQGRLPENVLLKELELVQNAFFTDPNDQSAWFYHRWLLGAG
SGRCELSVEKSTVLQSELESCKELQELEPENKWCLLTIILLMRALDPLLYEKETLQYFSTLKAVDPMRAAYLDDLRSKFL
LENSVLKMEYA

MGTQQKDVTIKSDAPDTLLLEKHADYIASYGSKKDDYEYCMSEYLRMSGVYWGLTVMDLMGQLHRMNKEEILVFIKSCQH
ECGGVSASIGHDPHLLYTLSAVQILTLYDSIHVINVDKVVAYVQSLQKEDGSFAGDIWGEIDTRFSFCAVATLALLGKLD
AINVEKAIEFVLSCMNFDGGFGCRPGSESHAGQIYCCTGFLAITSQLHQVNSDLLGWWLCERQLPSGGLNGRPEKLPDVC
YSWWVLASLKIIGRLHWIDREKLRSFILACQDEETGGFADRPGDMVDPFHTLFGIAGLSLLGEEQIKPVSPVFCMPEEVL
QRVNVQPELVS

coexpression of engineered alpha-subunit from pGATEV and beta-subunit from pET3 0a

14% (w/v) PEG 3350, 0.2M Ca(OAc)2, 0.1M HEPES, pH 7.2, VAPOR DIFFUSION, HANGING DROP, temperature 284K

Engineered RabGGTase in complex with a peptidomimetic inhibitor

RabGGTase(DELTA LRR; DELTA IG), apo form

RabGGTase(DELTA LRR; DELTA IG)in complex with geranylgeranyl pyrophosphate

RabGGTase(DELTA LRR; DELTA IG)in complex with farnesyl pyrophosphate

RabGGTase(DELTA LRR; DELTA IG)in complex with mono-prenylated peptide Ser-Cys-Ser-Cys(GG) derivated from Rab7

RabGGTase(DELTA LRR; DELTA IG)in complex with di-prenylated peptide Ser-Cys(GG)-Ser-Cys(GG) derivated from Rab7

THE DEPOSITORS HAVE SOAKED THE CRYSTALS WITH THE MONOPRENYLATED PEPTIDE SER-CYS(GG)-SER-CYS, BUT CAN ONLY SEE MINOR FRACTIONS OF THIS MOLECULE. GG IS GER (GERAN-8-YL GERAN) AND IS BOUND TO THE PENULTIMATE CYS. THE PEPTIDE IS DERIVED FROM RAB7.

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

protein prenylation, Metal-binding, Prenyltransferase, Transferase, Zinc, Phosphoprotein

MHGRLKVKTSEEQAEAKRLEREQKLKLYQSATQAVFQKRQAGELDESVLELTSQILGANPDFATLWNCRREVLQHLETEK
SPEESAALVKAELGFLESCLRVNPKSYGTWHHRCWLLSRLPEPNWARELELCARFLEADERNFHCWDYRRFVAAQAAVAP
AEELAFTDSLITRNFSNYSSWHYRSCLLPQLHPQPDSGPQGRLPENVLLKELELVQNAFFTDPNDQSAWFYHRWLLG

RCELSVEKSTVLQSELESCKELQELEPENKWCLLTIILLMRALDPLLYEKETLQYFSTLKAVDPMRAAYLDDLRSKFLLE
NSVLKMEYA