PDBsum entry 3kaf

Isomerase

PDB id

3kaf

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Contents

			Protein chain

					145 a.a. *

			Ligands

					4D9

			Waters ×48

* Residue conservation analysis

PDB id:

3kaf

Links
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Name:

Isomerase

Title:

Structure-guided design of alpha-amino acid-derived pin1 inhibitors

Structure:

Peptidyl-prolyl cis-trans isomerase nima-interacting 1. Chain: a. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.30Å

R-factor:

0.230

R-free:

0.312

Authors:

L.M.Baker,P.Dokurno,D.A.Robinson,A.E.Surgenor,J.B.Murray,A.J.Potter, J.D.Moore

Key ref:

A.J.Potter et al. (2010). Structure-guided design of alpha-amino acid-derived Pin1 inhibitors. Bioorg Med Chem Lett, 20, 586-590. PubMed id: 19969456

Date:

19-Oct-09

Release date:

22-Dec-09

PROCHECK

	Headers

	References

Protein chain

Q13526 (PIN1_HUMAN) - Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 from Homo sapiens

Seq: Struc:					163 a.a. 145 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.5.2.1.8 - peptidylprolyl isomerase.

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

Reaction:

[protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

Peptidylproline (omega=180)	=	peptidylproline (omega=0)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

	Bioorg Med Chem Lett 20:586-590 (2010)
PubMed id: 19969456

Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.
A.J.Potter, S.Ray, L.Gueritz, C.L.Nunns, C.J.Bryant, S.F.Scrace, N.Matassova, L.Baker, P.Dokurno, D.A.Robinson, A.E.Surgenor, B.Davis, J.B.Murray, C.M.Richardson, J.D.Moore.

ABSTRACT

The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) <100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21504850

L.Zhu, J.Jin, C.Liu, C.Zhang, Y.Sun, Y.Guo, D.Fu, X.Chen, and B.Xu (2011).
Synthesis and biological evaluation of novel quinazoline-derived human Pin1 inhibitors.

Bioorg Med Chem, 19, 2797-2807.

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.