Functional diversity among putative E2 isozymes in the mechanism of ubiquitin-histone ligation.

Haas, Amy L.; Bright, P M; Jackson, Vaughn

doi:10.1016/s0021-9258(18)37700-7

Cited by 100 publications

(15 citation statements)

References 45 publications

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“…In the Ub pathway, a single E1 enzyme (in yeast) sits at the top of the cascade, transferring Ub to many different E2s, one at a time. The fully loaded E1 has a high affinity for E2s, with dissociation constants (K d ) in the subnanomolar to nanomolar range depending on the E2 (Haas et al, 1988). However, the Ub-E1 only displays a low affinity for E2s in the absence of Ub and ATP, because E1 readily separates from the E2s during purification without ATP (Hershko et al, 1983).…”

Section: E2 Recognition: Specificity Element In the E1 Ufd-e2 Interfacementioning

confidence: 99%

Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes

Lee

Schindelin

2008

Cell

218

320

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Ubiquitin (Ub) and ubiquitin-like proteins (Ubls) are conjugated to their targets by specific cascades involving three classes of enzymes, E1, E2, and E3. Each E1 adenylates the C terminus of its cognate Ubl, forms a E1 approximately Ubl thioester intermediate, and ultimately generates a thioester-linked E2 approximately Ubl product. We have determined the crystal structure of yeast Uba1, revealing a modular architecture with individual domains primarily mediating these specific activities. The negatively charged C-terminal ubiquitin-fold domain (UFD) is primed for binding of E2s and recognizes their positively charged first alpha helix via electrostatic interactions. In addition, a mobile loop from the domain harboring the E1 catalytic cysteine contributes to E2 binding. Significant, experimentally observed motions in the UFD around a hinge in the linker connecting this domain to the rest of the enzyme suggest a conformation-dependent mechanism for the transthioesterification function of Uba1; however, this mechanism clearly differs from that of other E1 enzymes.

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Section: E2 Recognition: Specificity Element In the E1 Ufd-e2 Interfacementioning

confidence: 99%

Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes

Lee

Schindelin

2008

Cell

218

320

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“…The unstructured N-terminal tails are important features of the core histones since they serve as the primary regulatory sites by virtue of their susceptibility to an extensive array of covalent modifications. 44 A number of nuclear proteins are known to interact with amino acid residues along the N-terminal tails of linker and core histones, [45][46][47][48] allowing for modifier enzymes to add/remove acetate, 43,[49][50][51][52][53][54][55][56] ADP-ribose, 57 ubiquitin, [58][59][60] biotin, 61,62 phosphate, 63-65 SUMO, 66 methyl, [67][68][69][70][71] ethyl, 72 propyl, 72 and butyl 72 groups, along with other known 45,73 and yet-to-be-deciphered 72 posttranslational marks (Fig. 3).…”

Section: Epigenome Features 21 Histones and Their Modificationsmentioning

confidence: 99%

Epigenome manipulation as a pathway to new natural product scaffolds and their congeners

2010

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The covalent modification of chromatin is an important control mechanism used by fungi to modulate the transcription of genes involved in secondary metabolite production. To date, both molecularbased and chemical approaches targeting histone and DNA posttranslational processes have shown great potential for rationally directing the activation and/or suppression of natural-product-encoding gene clusters. In this Highlight, the organization of the fungal epigenome is summarized and strategies for manipulating chromatin-related targets are presented. Applications of these techniques are illustrated using several recently published accounts in which chemical-epigenetic methods and mutant studies were successfully employed for the de novo or enhanced production of structurally diverse fungal natural products (e.g

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“…Intersegm ental mu scle ext racts contained t hree major E2 thiol es te r bands th at migr a te d with or slightly below rabbit E2 14K , t he pr incipal isozym e present in reticul ocytes (2,35 ). Depending on running conditions, t hiol es te r gels ca n reveal spurious additional bands a rising from unfolding a rtifact s peculi ar to th e non-reducing SDS-PAGE sys te m (2,36). However , t he two thiol es ter bands migra ti ng just below t he reticulocyt e E2 14K sta nda rd are pr oba bly not runn ing ar tifacts since th eir a utora diographic intensities a re not pr opor tional to that comigr ating with t he reticulocyt e marker (Fig.…”

Section: Day -E1 T Ab Le I Effect Of 20-hy Droxyecdyso Ne On Intersegmenta L M Uscle Ubiquitin Pools and Rat Es Of Conj Uga Tio Nmentioning

confidence: 99%

Coordinated Induction of the Ubiquitin Conjugation Pathway Accompanies the Developmentally Programmed Death of Insect Skeletal Muscle

Haas

Baboshina

Williams

et al. 1995

Journal of Biological Chemistry

121

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The developmentally programmed cell death of abdominal intersegmental muscles in the tobacco hawk-moth Manduca sexta is coincident with a 10-fold induction of the polyubiquitin gene as a hormonally regulated event (Schwartz, L. M., Myer, A., Kosz, L., Engelstein, M., and Maier, C. (1990) Neuron 5, 411-419). Solid phase immunochemical assays measuring intersegmental muscle pools of free and conjugated ubiquitin reveal that the induction of polyubiquitin mRNA is accompanied by a proportional increase in total ubiquitin polypeptide. Ubiquitin conjugate pools increase 10-fold at eclosion, during which loss of muscle protein mass is maximum. A smaller but measurable increase in ubiquitin conjugates is observed earlier in pupal development coincident with a modest enhanced degradation of myofibrillar proteins. Accumulation of ubiquitin conjugates is accompanied by induction in the pathway for polypeptide ligation, including the activating enzyme (E1), several carrier protein (E2) isoforms, and ubiquitin:protein isopeptide ligase (E3). Both accumulation of ubiquitin polypeptide and the enzymes of the conjugation pathway are subject to regulation by declining titers of the insect molting hormone 20-hydroxyecdysone, which signals onset of programmed cell death in the intersegmental muscles. Thus, programmed cell death within the intersegmental muscles is accomplished in part by stimulation of the ubiquitin-mediated degradative pathway through a coordinated induction of ubiquitin and the enzymes responsible for its conjugation to yield proteolytic intermediates. This suggests enzymes required for ubiquitin conjugation may represent additional genes recruited for developmentally programmed death.

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Functional diversity among putative E2 isozymes in the mechanism of ubiquitin-histone ligation.

Cited by 100 publications

References 45 publications

Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes

Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes

Epigenome manipulation as a pathway to new natural product scaffolds and their congeners

Coordinated Induction of the Ubiquitin Conjugation Pathway Accompanies the Developmentally Programmed Death of Insect Skeletal Muscle

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