PDBsum entry 6ntp

Hydrolase

PDB id: 6ntp

Contents

Protein chain

281 a.a.

Metals

_MG

Waters ×224

PDB id:

6ntp

Name:

Hydrolase

Title:

Ptp1b domain of ptp1b-lov2 chimera

Structure:

Tyrosine-protein phosphatase non-receptor type 1,nph1-1. Chain: a. Fragment: residues 2-282. Synonym: protein-tyrosine phosphatase 1b,ptp-1b. Engineered: yes

Source:

Homo sapiens, avena sativa. Human, oat. Organism_taxid: 9606, 4498. Gene: ptpn1, ptp1b, nph1-1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.89Å R-factor: 0.181 R-free: 0.212

Authors:

A.Hongdusit,B.Sankaran,P.H.Zwart,J.M.Fox

Key ref:

A.Hongdusit et al. (2020). Minimally disruptive optical control of protein tyrosine phosphatase 1B. Nat Commun, 11, 788. PubMed id: 32034150 DOI: 10.1038/s41467-020-14567-8

Date:

30-Jan-19 Release date: 22-Jan-20

Protein chain

O49003  (O49003_AVESA) -  non-specific serine/threonine protein kinase from Avena sativa

Seq: 923 a.a.

Struc: 281 a.a.*

Protein chain

P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1 from Homo sapiens

Seq: 435 a.a.

Struc: 281 a.a.

* PDB and UniProt seqs differ at 201 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
• Enzyme class 2: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1038/s41467-020-14567-8

Nat Commun 11:788 (2020)

PubMed id: 32034150

Minimally disruptive optical control of protein tyrosine phosphatase 1B.

A.Hongdusit, P.H.Zwart, B.Sankaran, J.M.Fox.

ABSTRACT

Protein tyrosine phosphatases regulate a myriad of essential subcellular signaling events, yet they remain difficult to study in their native biophysical context. Here we develop a minimally disruptive optical approach to control protein tyrosine phosphatase 1B (PTP1B)-an important regulator of receptor tyrosine kinases and a therapeutic target for the treatment of diabetes, obesity, and cancer-and we use that approach to probe the intracellular function of this enzyme. Our conservative architecture for photocontrol, which consists of a protein-based light switch fused to an allosteric regulatory element, preserves the native structure, activity, and subcellular localization of PTP1B, affords changes in activity that match those elicited by post-translational modifications inside the cell, and permits experimental analyses of the molecular basis of optical modulation. Findings indicate, most strikingly, that small changes in the activity of PTP1B can cause large shifts in the phosphorylation states of its regulatory targets.