PDBsum entry 3h1d

Ligase

PDB id: 3h1d

Contents

Protein chain

382 a.a. *

Ligands

SO4 ×4

Waters ×357

* Residue conservation analysis

PDB id:

3h1d

Name:

Ligase

Title:

Structure of the huwe1 hect domain

Structure:

E3 ubiquitin-protein ligase huwe1. Chain: a. Fragment: hect. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: huwe1, kiaa0312, kiaa1578, ureb1, hspc272. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.89Å R-factor: 0.169 R-free: 0.229

Authors:

J.R.Partridge,T.U.Schwartz

Key ref:

R.K.Pandya et al. (2010). A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities. J Biol Chem, 285, 5664-5673. PubMed id: 20007713

Date:

11-Apr-09 Release date: 08-Dec-09

Protein chain

Q7Z6Z7  (HUWE1_HUMAN) -  E3 ubiquitin-protein ligase HUWE1 from Homo sapiens

Seq: 4374 a.a.

Struc: 382 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.2.26 - HECT-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

J Biol Chem 285:5664-5673 (2010)

PubMed id: 20007713

A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities.

R.K.Pandya, J.R.Partridge, K.R.Love, T.U.Schwartz, H.L.Ploegh.

ABSTRACT

E3 ubiquitin ligases catalyze the final step of ubiquitin conjugation and regulate numerous cellular processes. The HECT class of E3 ubiquitin (Ub) ligases directly transfers Ub from bound E2 enzyme to a myriad of substrates. The catalytic domain of HECT Ub ligases has a bilobal architecture that separates the E2 binding region and catalytic site. An important question regarding HECT domain function is the control of ligase activity and specificity. Here we present a functional analysis of the HECT domain of the E3 ligase HUWE1 based on crystal structures and show that a single N-terminal helix significantly stabilizes the HECT domain. We observe that this element modulates HECT domain activity, as measured by self-ubiquitination induced in the absence of this helix, as distinct from its effects on Ub conjugation of substrate Mcl-1. Such subtle changes to the protein may be at the heart of the vast spectrum of substrate specificities displayed by HECT domain E3 ligases.