2hlw

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[[Image:2hlw.gif|left|200px]]
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{{STRUCTURE_2hlw| PDB=2hlw | SCENE= }}
{{STRUCTURE_2hlw| PDB=2hlw | SCENE= }}
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'''Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a'''
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===Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16893187 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16893187}}
==About this Structure==
==About this Structure==
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2HLW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HLW OCA].
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2HLW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HLW OCA].
==Reference==
==Reference==
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[[Category: Ubiquitin]]
[[Category: Ubiquitin]]
[[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 Sun May 4 06:26:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:08:26 2008''

Revision as of 06:08, 29 July 2008

Template:STRUCTURE 2hlw

Solution Structure of the Human Ubiquitin-conjugating Enzyme Variant Uev1a

Template:ABSTRACT PUBMED 16893187

About this Structure

2HLW is a Single protein structure of sequence from Homo sapiens. Full experimental 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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