2hlw

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|ACTIVITY=
|ACTIVITY=
|GENE= UEV1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= UEV1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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|RELATEDENTRY=[[2a4d|2A4D]], [[2c2v|2C2V]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hlw OCA], [http://www.ebi.ac.uk/pdbsum/2hlw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hlw RCSB]</span>
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[[Category: ubiquitin-conjugating enzyme variant]]
[[Category: ubiquitin-conjugating enzyme variant]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:18:37 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:32:14 2008''

Revision as of 00:32, 31 March 2008


PDB ID 2hlw

Drag the structure with the mouse to rotate
Gene: UEV1 (Homo sapiens)
Related: 2A4D, 2C2V


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a


Overview

Lys(63)-linked polyubiquitination of TRAF2 or TRAF6 is an essential step within the signal transduction cascade responsible for activation of p38, c-Jun N-terminal kinase, and the transcription factor NF-kappaB. Attachment of ubiquitin (Ub) to a TRAF, and conjugation of Ub molecules to form a polyUb chain, is catalyzed by a heterodimer composed of a catalytically active E2 (hUbc13), involved in covalent bond transfer, and hUev1a, an E2-like protein involved in substrate Ub binding. Given the key biochemical processes in which hUev1a is involved, it is important to determine the molecular basis of the catalytic mechanism for Lys(63)-linked protein ubiquitination. Nuclear magnetic resonance (NMR) spectroscopy was used to determine the structure of hUev1a and its interactions with Ub and hUbc13. A structural model for the Ub-hUev1a-hUbc13-Ub tetramer was developed to gain chemical insight into the synthesis of Lys(63)-linked Ub chains. We propose that a network of hydrogen bonds involving hUbc13-Asp(81) and Ub-Glu(64) positions Ub-Lys(63) proximal to the active site. Interestingly, restrained molecular dynamics simulations in implicit solvent indicate that deprotonation of Ub-Lys(63) does not involve a general Asp or Glu base and may occur when the amino group approaches the thioester carbonyl carbon near the Burgi-Dunitz trajectory.

About this Structure

2HLW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure and interactions of the ubiquitin-conjugating enzyme variant human Uev1a: implications for enzymatic synthesis of polyubiquitin chains., Hau DD, Lewis MJ, Saltibus LF, Pastushok L, Xiao W, Spyracopoulos L, Biochemistry. 2006 Aug 15;45(32):9866-77. PMID:16893187

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