PDBsum entry 5o2p

Structure from cyana 3.97

PDB id: 5o2p

Contents

Protein chain

100 a.a.

PDB id:

5o2p

Name:

Structure from cyana 3.97

Title:

P130cas sh3 domain ptp-pest peptide chimera

Structure:

Breast cancer anti-estrogen resistance 1,tyrosine-protein phosphatase non-receptor type 12. Chain: a. Synonym: cas sh3 domain ptp-pest peptide chimera,ptp-pest,protein- tyrosine phosphatase g1,ptpg1,cas sh3 domain ptp-pest peptide chimera. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bcar1, ptpn12. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

40 models

Authors:

R.Hexnerova,V.Veverka

Key ref:

J.Gemperle et al. (2017). Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners. Sci Rep, 7, 8057. PubMed id: 28808245

Date:

22-May-17 Release date: 20-Sep-17

Protein chain

P56945  (BCAR1_HUMAN) -  Breast cancer anti-estrogen resistance protein 1 from Homo sapiens

Seq: 870 a.a.

Struc: 100 a.a.*

Protein chain

Q05209  (PTN12_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 12 from Homo sapiens

Seq: 780 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 102 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

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

Key reference

Sci Rep 7:8057 (2017)

PubMed id: 28808245

Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.

J.Gemperle, R.Hexnerová, M.Lepšík, P.Tesina, M.Dibus, M.Novotný, J.Brábek, V.Veverka, D.Rosel.

ABSTRACT

CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.