X-ray structure of PTP1B in complex with a new PTP1B inhibitor

M. V V V Sekhar Reddy, Chakshumathi Ghadiyaram, Sunil Kumar Panigrahi, Narasimha Rao Krishnamurthy, Subramanya Hosahalli, Arun P. Chandrasekharappa, Dipankar Manna, Sangamesh E. Badiger, Pramod K. Dubey, Lakshmi Narasu Mangamoori

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a prototype non receptor cytoplasmic PTPase enzyme that has been implicated in regulation of insulin and leptin signaling pathways. Studies on PTP1B knockout mice and PTP1B antisense treated mice suggested that inhibition of PTP1B would be an effective strategy for the treatment of type II diabetes and obesity. Here we report the X-ray structure of PTP1B in complex with compound IN1834-146C (PDB ID 4I8N). The crystals belong to P3121 space group with cell dimensions (a = b = 87.89 Å, c = 103.68 Å) diffracted to 2.5 Å. The crystal structure contained one molecule of protein in the asymmetric unit and was solved by molecular replacement method. The compound engages both catalytic site and allosteric sites of PTP1B protein. We described the molecular interaction of the compound with the active site residues of PTP1B in this crystal structure report.

Original languageEnglish (US)
Pages (from-to)90-93
Number of pages4
JournalProtein and Peptide Letters
Volume21
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
X-Rays
X rays
Catalytic Domain
Crystal structure
Allosteric Site
Protein Tyrosine Phosphatases
Molecular interactions
Cytoplasmic and Nuclear Receptors
Medical problems
Leptin
Knockout Mice
Type 2 Diabetes Mellitus
Proteins
Obesity
Insulin
Crystals
Molecules
Enzymes

Keywords

  • Protein tyrosine phosphatases (PTP1B)
  • T cell PTP (TCPTP) and X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology

Cite this

Reddy, M. V. V. V. S., Ghadiyaram, C., Panigrahi, S. K., Krishnamurthy, N. R., Hosahalli, S., Chandrasekharappa, A. P., ... Mangamoori, L. N. (2014). X-ray structure of PTP1B in complex with a new PTP1B inhibitor. Protein and Peptide Letters, 21(1), 90-93. https://doi.org/10.2174/09298665113209990089

X-ray structure of PTP1B in complex with a new PTP1B inhibitor. / Reddy, M. V V V Sekhar; Ghadiyaram, Chakshumathi; Panigrahi, Sunil Kumar; Krishnamurthy, Narasimha Rao; Hosahalli, Subramanya; Chandrasekharappa, Arun P.; Manna, Dipankar; Badiger, Sangamesh E.; Dubey, Pramod K.; Mangamoori, Lakshmi Narasu.

In: Protein and Peptide Letters, Vol. 21, No. 1, 01.2014, p. 90-93.

Research output: Contribution to journalArticle

Reddy, MVVVS, Ghadiyaram, C, Panigrahi, SK, Krishnamurthy, NR, Hosahalli, S, Chandrasekharappa, AP, Manna, D, Badiger, SE, Dubey, PK & Mangamoori, LN 2014, 'X-ray structure of PTP1B in complex with a new PTP1B inhibitor', Protein and Peptide Letters, vol. 21, no. 1, pp. 90-93. https://doi.org/10.2174/09298665113209990089
Reddy MVVVS, Ghadiyaram C, Panigrahi SK, Krishnamurthy NR, Hosahalli S, Chandrasekharappa AP et al. X-ray structure of PTP1B in complex with a new PTP1B inhibitor. Protein and Peptide Letters. 2014 Jan;21(1):90-93. https://doi.org/10.2174/09298665113209990089
Reddy, M. V V V Sekhar ; Ghadiyaram, Chakshumathi ; Panigrahi, Sunil Kumar ; Krishnamurthy, Narasimha Rao ; Hosahalli, Subramanya ; Chandrasekharappa, Arun P. ; Manna, Dipankar ; Badiger, Sangamesh E. ; Dubey, Pramod K. ; Mangamoori, Lakshmi Narasu. / X-ray structure of PTP1B in complex with a new PTP1B inhibitor. In: Protein and Peptide Letters. 2014 ; Vol. 21, No. 1. pp. 90-93.
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