PDBsum entry 2gv2

Ligase

PDB id

2gv2

Loading ...

Contents

			Protein chain

					88 a.a. *

			Ligands

					ACE-PHE-MET-AIB- PM3-6CW-GLU-1AC- LEU

			Waters ×93

* Residue conservation analysis

PDB id:

2gv2

Links

Name:

Ligase

Title:

Mdm2 in complex with an 8-mer p53 peptide analogue

Structure:

E3 ubiquitin-protein ligase mdm2. Chain: a. Fragment: p53 binding domain (residues: 17-125). Engineered: yes. 8-mer p53 peptide analogue. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mdm2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide

Resolution:

1.80Å

R-factor:

0.195

R-free:

0.219

Authors:

C.Schubert,K.Sakurai

Key ref:

K.Sakurai et al. (2006). Crystallographic analysis of an 8-mer p53 peptide analogue complexed with MDM2. J Am Chem Soc, 128, 11000-11001. PubMed id: 16925398 DOI: 10.1021/ja063102j

Date:

02-May-06

Release date:

05-Sep-06

PROCHECK

	Headers

	References

Protein chain

P06704 (CDC31_YEAST) - Cell division control protein 31 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: Struc:					161 a.a. 88 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 70 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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: 10.1021/ja063102j	J Am Chem Soc 128:11000-11001 (2006)
PubMed id: 16925398

Crystallographic analysis of an 8-mer p53 peptide analogue complexed with MDM2.
K.Sakurai, C.Schubert, D.Kahne.

ABSTRACT

The most potent inhibitor of the p53-MDM2 interaction reported to date is an 8-mer p53 peptide analogue (Novartis peptide), which contains 6-chlorotryptophane (Cl-Trp) and phosphonomethylphenylalanine (Pmp) as key residues for the enhanced activity. We report here a crystal structure of the co-complex between MDM2 and the Novartis peptide solved at 1.8 A resolution. The structural basis for the role of the two aromatic residues are delineated by comparing the present structure with crystal structures of the MDM2 co-complex bound to other inhibitors including the wt-p53 peptide itself.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20882600

D.A.Guarracino, B.N.Bullock, and P.S.Arora (2011).
Protein-protein interactions in transcription: A fertile ground for helix mimetics.

Biopolymers, 95, 1-7.

20821791

L.K.Henchey, J.R.Porter, I.Ghosh, and P.S.Arora (2010).
High specificity in protein recognition by hydrogen-bond-surrogate α-helices: selective inhibition of the p53/MDM2 complex.

Chembiochem, 11, 2104-2107.

19408261

A.Grässlin, C.Amoreira, K.K.Baldridge, and J.A.Robinson (2009).
Thermodynamic and computational studies on the binding of p53-derived peptides and peptidomimetic inhibitors to HDM2.

Chembiochem, 10, 1360-1368.

19153082

J.Kallen, A.Goepfert, A.Blechschmidt, A.Izaac, M.Geiser, G.Tavares, P.Ramage, P.Furet, K.Masuya, and J.Lisztwan (2009).
Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues Reveal Surprising Conformational Changes.

J Biol Chem, 284, 8812-8821.

PDB codes:

3fe7 3fea

19021159

M.Orzáez, A.Gortat, L.Mondragón, and E.Pérez-Payá (2009).
Peptides and peptide mimics as modulators of apoptotic pathways.

ChemMedChem, 4, 146-160.

19255450

M.Pazgier, M.Liu, G.Zou, W.Yuan, C.Li, C.Li, J.Li, J.Monbo, D.Zella, S.G.Tarasov, and W.Lu (2009).
Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX.

Proc Natl Acad Sci U S A, 106, 4665-4670.

PDB codes:

3eqs 3eqy

19642417

R.C.Clark, S.Y.Lee, M.Searcey, and D.L.Boger (2009).
The isolation, total synthesis and structure elucidation of chlorofusin, a natural product inhibitor of the p53-mDM2 protein-protein interaction.

Nat Prod Rep, 26, 465-477.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.