PDBsum entry 3vk6

Ligase

PDB id: 3vk6

Contents

Protein chain

96 a.a.

Metals

_ZN ×3

Waters ×70

PDB id:

3vk6

Name:

Ligase

Title:

Crystal structure of a phosphotyrosine binding domain

Structure:

E3 ubiquitin-protein ligase hakai. Chain: a. Fragment: phosphotyrosine binding domain, unp residues 106-206. Synonym: casitas b-lineage lymphoma-transforming sequence-like protein 1, e-cadherin binding protein e7, c-cbl-like protein 1. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cbll1, hakai. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.222 R-free: 0.242

Authors:

J.Sivaraman,M.Mukherjee

Key ref:

M.Mukherjee et al. (2012). Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. Embo J, 31, 1308-1319. PubMed id: 22252131

Date:

09-Nov-11 Release date: 25-Jan-12

Protein chain

Q9JIY2  (HAKAI_MOUSE) -  E3 ubiquitin-protein ligase Hakai from Mus musculus

Seq: 491 a.a.

Struc: 96 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-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

Embo J 31:1308-1319 (2012)

PubMed id: 22252131

Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin.

M.Mukherjee, S.Y.Chow, P.Yusoff, J.Seetharaman, C.Ng, S.Sinniah, X.W.Koh, N.F.Asgar, D.Li, D.Yim, R.A.Jackson, J.Yew, J.Qian, A.Iyu, Y.P.Lim, X.Zhou, S.K.Sze, G.R.Guy, J.Sivaraman.

ABSTRACT

Phosphotyrosine-binding domains, typified by the SH2 (Src homology 2) and PTB domains, are critical upstream components of signal transduction pathways. The E3 ubiquitin ligase Hakai targets tyrosine-phosphorylated E-cadherin via an uncharacterized domain. In this study, the crystal structure of Hakai (amino acids 106-206) revealed that it forms an atypical, zinc-coordinated homodimer by utilizing residues from the phosphotyrosine-binding domain of two Hakai monomers. Hakai dimerization allows the formation of a phosphotyrosine-binding pocket that recognizes specific phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. NMR and mutational analysis identified the Hakai residues required for target binding within the binding pocket, now named the HYB domain. ZNF645 also possesses a HYB domain but demonstrates different target specificities. The HYB domain is structurally different from other phosphotyrosine-binding domains and is a potential drug target due to its novel structural features.