IndraLab

Statements

UCHL3 binds Ubiquitin. 35 / 39
| 2 33
sparser
"One possibility for the enhanced discrimination of Gly over Val at P2 in the context of the natural substrate is that ubiquitin binding to UCH-L3 may help to position its P2 residue for optimal catalysis."
18601651
sparser
"Building on our previous work for computational development of UCH selective UbV-ABPs, we applied a rational design approach to incorporate mutations to the Ub-UCHL3 protein-protein interaction (PPI) interface that would improve binding affinity and impart selectivity over UCHL1 and other DUBs."
35053210
sparser
"Both ABPs were shown to interact with UCHL3 as indicated by the presence of the higher molecular weight band correlating to the UCHL3-Ub complex formation over the time course."
35053210
sparser
"To do this a binding analysis of the interactions at the PPI interface of both the Ub-UCHL3 (PDB: 1XD3 [ xref ]) and Ub-UCHL1 (PDB: 3KW5 [ xref ]) crystal structure complexes was carried out using BioLuminate (Schrödinger, LLC, New York, NY, USA) in an effort to identify interactions Ub makes that are different between the two DUBs."
35053210
sparser
"Binding of ubiquitin leads to apparent stabilization of the crossover loop, as it was seen straddling the active site in co-crystal structures of ubiquitin aldehyde bound to UCHL3 ( xref and xref ) and the yeast UCH Yuh1 xref , xref ."
27012468
sparser
"From a crystal structure of a complex between UCHL3 and synthetic K27 Ub 2 , we unexpectedly discover that free K27 Ub 2 and K27 Ub 2 -conjugated substrates are natural inhibitors of UCHL3."
33238157
reach
"We identified three inhibitors (IC 50 = 100–150 μM) of UCH-L3 by the DOCK–GOLD virtual screening of 32,799 compounds.In the 3D structure of the UCH-L3-ubiquitin complex, ubiquitin C-terminus is buried[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17761421
sparser
"Isotopically labelled ubiquitin was bound to excess UCH-L3 and the chemical shift changes relative to free ubiquitin were determined."
10518943
sparser
"NMR assignments ( 1 HN, 15 N, 13 C α , 13 CO) were determined for 2 H, 13 C, 15 N-labeled human ubiquitin bound to UCH-L3."
10518943
sparser
"From the structure of UCHL3 WT -Ub-VME, we can see that Pro8 on UCHL3 interacts with Arg74 on Ub via hydrogen bonding."
36142702
sparser
"While almost all of the chemical shifts for the N-terminal 70 amino acid residues of 2 H, 13 C, 15 N-labeled ubiquitin bound to UCH-L3 were assigned, some resonances remained unassigned, including [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10518943
sparser
"We have previously noted that the interaction between ubiquitin and UCH-L3 was ablated by high salt (Larsen et al ., 1996) , suggesting that the interactions were primarily electrostatic."
10518943
sparser
"Next we quantified the change in chemical shift induced upon binding of ubiquitin to UCH-L3."
10518943
sparser
"To determine if these electrostatic interactions contribute significantly to the stability of the ubiquitin·UCH-L3 complex, we mutated a number of basic residues on the surface of ubiquitin and measur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10518943
sparser
"Having defined the surface of ubiquitin that interacts with UCH-L3, we next sought to identify candidate residues on UCH-L3 that interact with ubiquitin."
10518943
sparser
"Residues 10–14, 33–36, 167–168 and 219–223 on UCH-L3 (see below) all form close interactions with ubiquitin."
10518943
sparser
"Meanwhile, the hydrophobic interaction between Arg 72 on Ub and Gln 12 on UCHL3 and the hydrogen bond between Ala11 on UCHL3 and Leu73 on Ub become stronger after phosphorylation, which may play a role in the recognition of the substrate by UCHL3 ( xref D,E)."
36142702
sparser
"Yeast OTU1, for instance, shows no binding up to 2 mM ubiquitin while UCH-L3 binds ubiquitin with an affinity of 100–500 μM. As in other DUBs, the affinity of ataxin-3 will be increased by avidity thanks to the multiple binding sites, thus explaining the need of such redundancy."
25988170
sparser
"In contrast, when UCH-L3 is bound to an ubiquitin-based inhibitor, ubiquitin vinyl methyl ester, the crossover loop becomes stabilized in an α-helix followed by an S shaped loop forming contacts with the C terminus of ubiquitin ( xref )."
19489724
sparser
"Since ubiquitin binding orders a significant portion of the protein, the UCH domain of BAP1 was modeled after Uch-L3 bound to ubiquitin (PDB: 1xd3)."
22683710
sparser
"Binding of mutant ubiquitin to UCH-L3 was by determining the inhibition constant of the mutant as a competitive inhibitor of 125 I-labeled Y77Ub processing."
10518943
sparser
"Analysis of UCHL3 mutants showed that the aspartic acid residue at position 33 and the cysteine residue at position 95 are key sites for the interaction between UCHL3 and ubiquitin. xref To restore the knockdown effects of UCHL3 shRNAs, we re-expressed wild-type UCHL3 and the inactive mutants UCHL3-C95S and UCHL3-D33A in H358 cells with stable UCHL3 knockdown."
32546741
sparser
"Information for structures was from the protein data bank (PDB): ubiquitin from UCH-L3-Ub complex (PDB code: 1XD3) and ISG15 (PDB code: 1Z2M)."
20153823
sparser
"The phosphorylation site Ser75 of UCHL3 is located on S1′, and phosphorylation of Ser75 may help S1′ to form the correct conformation and enhance the interaction between ubiquitin chains and UCHL3."
36142702
sparser
"A model for ubiquitin binding to YUH1 is proposed, in which a good correlation was observed for the lateral binding of ubiquitin to UCH-L3 (YUH1), stabilized by the electrostatic and hydrophobic interactions."
10413498
sparser
"In the 3D structure of the UCH-L3-ubiquitin complex, ubiquitin C-terminus is buried in the active site cleft among four active site residues of UCH-L3: Gln89, Cys95, His169, and Asp184."
17761421
sparser
"Thermodynamic parameters of UCHL3–ubiquitin interactions were found to be K d value of ~0.01 µM, ΔH ~ –49.6 kJ/mol, ΔS ~ –14.9 J/mol·K, and ΔG ~ –45.3 kJ M −1 ( xref ) which was consistent with the K m value reported earlier."
28935764
sparser
"Hydrolysis activity of UCH-L3 is inhibited if a compound binds to its active site and thus blocks interaction between the active site of UCH-L3 and the ubiquitin C-terminus."
17761421
sparser
"17 Hydrogens were added to UCH-L3-ubiquitin complex using CVFF99 force field by Biopolymer module in Insight II 2000 suite (Accelrys, Inc., San Diego, CA)."
17761421
sparser
"Ubiquitin binds to a short peptide segment of hydrolase UCH-L3: a study by FCS, RIfS, ITC and NMR."
17211910
reach
"Furthermore, X-ray crystal structures of Ub bound to UCH-L3 reveal extensive protein protein interactions that may only exist in the native folded form of Ub (XREF_SUPPLEMENTARY)."
24838693
sparser
"Yeast OTU1 shows no binding up to 2 mM ubiquitin, UCH-L3 binds ubiquitin with an affinity of 100-500 μ M and USP5 binds with a Kd of 50 nM."
19243136
sparser
"Based upon analogy with inhibitor complexes of the papain-like enzymes, we propose a model describing the binding of ubiquitin to UCH-L3."
9233788
sparser
"Furthermore, X-ray crystal structures of Ub bound to UCH-L3 reveal extensive protein-protein interactions that may only exist in the native folded form of Ub ( xref ).[ xref ]Thus, our methodology yields site-specifically ubiquitylated and SUMOylated peptides that adopt a native fold and are suitable for in vitro biochemical studies."
24838693
sparser
"The high preference at the P3 position and relatively low specificity in the P4 position can be explained by comparison with the published crystal structure of UCH-L3 bound with ubiquitin inhibitor ( xref )."
18601651