1uch
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Ubiquitin C-terminal hydrolases catalyze the removal of adducts from the | + | Ubiquitin C-terminal hydrolases catalyze the removal of adducts from the C-terminus of ubiquitin. We have determined the crystal structure of the recombinant human Ubiquitin C-terminal Hydrolase (UCH-L3) by X-ray crystallography at 1.8 A resolution. The structure is comprised of a central antiparallel beta-sheet flanked on both sides by alpha-helices. The beta-sheet and one of the helices resemble the well-known papain-like cysteine proteases, with the greatest similarity to cathepsin B. This similarity includes the UCH-L3 active site catalytic triad of Cys95, His169 and Asp184, and the oxyanion hole residue Gln89. Papain and UCH-L3 differ, however, in strand and helix connectivity, which in the UCH-L3 structure includes a disordered 20 residue loop (residues 147-166) that is positioned over the active site and may function in the definition of substrate specificity. Based upon analogy with inhibitor complexes of the papain-like enzymes, we propose a model describing the binding of ubiquitin to UCH-L3. The UCH-L3 active site cleft appears to be masked in the unliganded structure by two different segments of the enzyme (residues 9-12 and 90-94), thus implying a conformational change upon substrate binding and suggesting a mechanism to limit non-specific hydrolysis. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ubiquitin thiolesterase]] | [[Category: Ubiquitin thiolesterase]] | ||
| - | [[Category: Cook, W | + | [[Category: Cook, W J.]] |
| - | [[Category: Hill, C | + | [[Category: Hill, C P.]] |
| - | [[Category: Johnston, S | + | [[Category: Johnston, S C.]] |
| - | [[Category: Larsen, C | + | [[Category: Larsen, C N.]] |
| - | [[Category: Wilkinson, K | + | [[Category: Wilkinson, K D.]] |
[[Category: c-terminal hydrolase]] | [[Category: c-terminal hydrolase]] | ||
[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
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[[Category: ubiquitin conjugation]] | [[Category: ubiquitin conjugation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:58 2008'' |
Revision as of 13:22, 21 February 2008
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DEUBIQUITINATING ENZYME UCH-L3 (HUMAN) AT 1.8 ANGSTROM RESOLUTION
Overview
Ubiquitin C-terminal hydrolases catalyze the removal of adducts from the C-terminus of ubiquitin. We have determined the crystal structure of the recombinant human Ubiquitin C-terminal Hydrolase (UCH-L3) by X-ray crystallography at 1.8 A resolution. The structure is comprised of a central antiparallel beta-sheet flanked on both sides by alpha-helices. The beta-sheet and one of the helices resemble the well-known papain-like cysteine proteases, with the greatest similarity to cathepsin B. This similarity includes the UCH-L3 active site catalytic triad of Cys95, His169 and Asp184, and the oxyanion hole residue Gln89. Papain and UCH-L3 differ, however, in strand and helix connectivity, which in the UCH-L3 structure includes a disordered 20 residue loop (residues 147-166) that is positioned over the active site and may function in the definition of substrate specificity. Based upon analogy with inhibitor complexes of the papain-like enzymes, we propose a model describing the binding of ubiquitin to UCH-L3. The UCH-L3 active site cleft appears to be masked in the unliganded structure by two different segments of the enzyme (residues 9-12 and 90-94), thus implying a conformational change upon substrate binding and suggesting a mechanism to limit non-specific hydrolysis.
About this Structure
1UCH is a Single protein structure of sequence from Homo sapiens. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution., Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP, EMBO J. 1997 Jul 1;16(13):3787-96. PMID:9233788
Page seeded by OCA on Thu Feb 21 15:22:58 2008
