PDBsum entry 1nd7

Ligase

PDB id: 1nd7

Contents

Protein chain

374 a.a. *

* Residue conservation analysis

PDB id:

1nd7

Name:

Ligase

Title:

Conformational flexibility underlies ubiquitin ligation mediated by the wwp1 hect domain e3 ligase

Structure:

Ww domain-containing protein 1. Chain: a. Fragment: wwp1 hect domain. Synonym: wwp1 hect domain, suppressor of deltex related protein 1, nedd-4-like ubiquitin-protein ligase, atrophin-1 interacting protein 5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wwp1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.10Å R-factor: 0.243 R-free: 0.270

Authors:

M.A.Verdecia,C.A.P.Joaziero,N.J.Wells,J.-L.Ferrer,M.E.Bowman, T.Hunter,J.P.Noel

Key ref:

M.A.Verdecia et al. (2003). Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. Mol Cell, 11, 249-259. PubMed id: 12535537 DOI: 10.1016/S1097-2765(02)00774-8

Date:

08-Dec-02 Release date: 23-Sep-03

Protein chain

Q9H0M0  (WWP1_HUMAN) -  NEDD4-like E3 ubiquitin-protein ligase WWP1 from Homo sapiens

Seq: 922 a.a.

Struc: 374 a.a.*

* PDB and UniProt seqs differ at 2 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

DOI no: 10.1016/S1097-2765(02)00774-8

Mol Cell 11:249-259 (2003)

PubMed id: 12535537

Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.

M.A.Verdecia, C.A.Joazeiro, N.J.Wells, J.L.Ferrer, M.E.Bowman, T.Hunter, J.P.Noel.

ABSTRACT

Ubiquitin ligases (E3) select proteins for ubiquitylation, a modification that directs altered subcellular trafficking and/or degradation of the target protein. HECT domain E3 ligases not only recognize, but also directly catalyze, ligation of ubiquitin to their protein substrates. The crystal structure of the HECT domain of the human ubiquitin ligase WWP1/AIP5 maintains a two-lobed structure like the HECT domain of the human ubiquitin ligase E6AP. While the individual N and C lobes of WWP1 possess very similar folds to those of E6AP, the organization of the two lobes relative to one another is different from E6AP due to a rotation about a polypeptide hinge linking the N and C lobes. Mutational analyses suggest that a range of conformations achieved by rotation about this hinge region is essential for catalytic activity.

Selected figure(s)

Figure 5.
Figure 5. Stabilizing Interactions at the Base of the Hinge Loop(A) Residue contacts within E6AP in the L shape conformation. Lys549 interacts with Asn822, Gln553 hydrogen bonds with Thr819, and Asp607 appears to interact with His609.(B) Residue contacts within WWP1/AIP5 in the shape conformation. Arg613 interacts with Gly610, and His621 hydrogen bonds with Asp675. Both pairs of interactions bridge the H3 helix to loop regions (S2/H3 and H4/H5 loops).(C) WWP1/AIP5 (residues 546–922) was used as a reference for wild-type autoubiquitylation activity.

Figure 6.
Figure 6. C Lobe and N Lobe Interactions in WWP1/AIP5(A) Residue contacts between the N and C lobes within WWP1/AIP5 in the shape conformation. Asp793 on the N lobe interacts with Arg845 on the C lobe. Gln848 and Arg855 on the C lobe form hydrogen bonds with Glu798 and the carbonyl oxygen of Thr676. Asp793 and Arg845 are highly conserved, and Glu798, Gln848, and Arg855 are absolutely conserved among 22 HECT domain sequences analyzed (data not shown).(B) Ubiquitin transfer assays.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 11, 249-259) copyright 2003.

Figures were selected by an automated process.