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PDBsum entry 5o6c
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PDB id:
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Ligase
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Title:
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Crystal structure of a threonine-selective rcr e3 ligase
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Structure:
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E3 ubiquitin-protein ligase mycbp2. Chain: a. Synonym: myc-binding protein 2,pam/highwire/rpm-1 protein,protein associated with myc,ring-type e3 ubiquitin transferase mycbp2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mycbp2, kiaa0916, pam. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.75Å
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R-factor:
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0.172
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R-free:
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0.196
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Authors:
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K.-C.Pao,K.Z.Rafie,D.Van Aalten,S.Virdee
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Key ref:
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K.C.Pao
et al.
(2018).
Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.
Nature,
556,
381-385.
PubMed id:
DOI:
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Date:
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06-Jun-17
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Release date:
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18-Apr-18
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PROCHECK
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Headers
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References
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O75592
(MYCB2_HUMAN) -
E3 ubiquitin-protein ligase MYCBP2 from Homo sapiens
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Seq:
Struc:
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4678 a.a.
252 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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Enzyme class:
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E.C.2.3.2.33
- RCR-type E3 ubiquitin transferase.
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Reaction:
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine
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DOI no:
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Nature
556:381-385
(2018)
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PubMed id:
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Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.
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K.C.Pao,
N.T.Wood,
A.Knebel,
K.Rafie,
M.Stanley,
P.D.Mabbitt,
R.Sundaramoorthy,
K.Hofmann,
D.M.F.van Aalten,
S.Virdee.
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ABSTRACT
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Ubiquitination is initiated by transfer of ubiquitin (Ub) from a
ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2),
producing a covalently linked intermediate (E2-Ub) 1 . Ubiquitin
ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub
via their RING domain and then mediate direct transfer of ubiquitin to
substrates 2 . By contrast, 'homologous to E6-AP carboxy terminus'
(HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation
reaction with E2-Ub, forming a covalent E3-Ub intermediate3,4.
Additionally, RING-between-RING (RBR) E3 ligases have a canonical RING domain
that is linked to an ancillary domain. This ancillary domain contains a
catalytic cysteine that enables a hybrid RING-HECT mechanism 5 .
Ubiquitination is typically considered a post-translational modification of
lysine residues, as there are no known human E3 ligases with non-lysine
activity. Here we perform activity-based protein profiling of HECT or RBR-like
E3 ligases and identify the neuron-associated E3 ligase MYCBP2 (also known as
PHR1) as the apparent single member of a class of RING-linked E3 ligase with
esterification activity and intrinsic selectivity for threonine over serine.
MYCBP2 contains two essential catalytic cysteine residues that relay ubiquitin
to its substrate via thioester intermediates. Crystallographic characterization
of this class of E3 ligase, which we designate RING-Cys-relay (RCR), provides
insights into its mechanism and threonine selectivity. These findings implicate
non-lysine ubiquitination in cellular regulation of higher eukaryotes and
suggest that E3 enzymes have an unappreciated mechanistic diversity.
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