2hlw
From Proteopedia
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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
Page seeded by OCA on Mon Nov 12 22:34:01 2007
