Madan Laboratory - Publications

Proteins: Motion, Mechanism, Meaning

Link to lab publications:

GOOGLE SCHOLAR: https://scholar.google.co.in/citations?user=PnM5oyUAAAAJ&hl=en

RESEARCH GATE: https://www.researchgate.net/profile/Lalima-K-Madan

Overview of our research using selected figures from publications:

FIGURE 6: Structural comparison of F225 equivalent position in PTP1B and SHP2.

Top panels show the overall domain architecture of PTP1B (left) and SHP2 (right). PTP1B consists of a single catalytic PTP domain, while SHP2 contains two N-terminal SH2 domains (N-SH2 in purple, C-SH2 in light green) in addition to the PTP catalytic domain (cyan). C215 (PTP1B) and C459 (SHP2) in the active site are shown in yellow at equivalent positions. Bottom panels show a detailed view of the aromatic cluster surrounding F225/F469 in WPD-open conformations. Left: PTP1B showing F225 (green, asterisk) in static “down” conformation, forming an aromatic network with F191 and F194, with catalytic cysteine C215 (yellow) and catalytic aspartate D181. Right: SHP2 showing F469 (cyan, asterisk) at the equivalent position with V435 replacing F191, F438 corresponding to F194, catalytic C459 (yellow), and catalytic D425. Despite similar local architecture, F469 exhibits conformational flexibility (dual occupancy) not observed in PTP1B F225, indicating subfamily-specific regulatory mechanisms. This distinct conformational behavior at equivalent positions may provide a structural basis for designing subfamily-selective allosteric inhibitors that could differentially target PTP1B for diabetes versus SHP2 for cancer.

https://onlinelibrary.wiley.com/doi/10.1002/prot.70169

Fig 2. Protein Tyrosine Phosphatases as negative and positive regulators of phosphorylation based signaling.
Adv Cancer Res 2021;152:263-303. PMID: 34353440 PMCID: PMC10544742

Fig 6. Community network at the activation segment of the 7 kinase:peptide complexes. The community network at activation segment is seen to vary in the 7 kinase:peptide complexes in accordance with the signatures of their molecular recognition.

Proc Natl Acad Sci U S A 2019 Jul 23;116(30):15052-15061. PMID: 31285328 PMCID: PMC6660753

Fig 2. The conserved kinase core harbors a hydrophobic motif known as the regulatory or R-spine. An assembled R-spine is the signature of the “active” kinase conformation. This assembly and disassembly of the R-spine in accordance with effects like activation loop phosphorylation and kinase dimerization forms a conformation-based allosteric descriptor of protein kinase activation.

IUBMB Life 2019 Jun;71(6):685-696. PMID: 31063633 PMCID: PMC6690483

Fig 4. Dynamics of pseudosubstrate binding at the PKA active-site cleft. (A) Pseudosubstrate peptide interacting residues at the PKA active-site cleft. (B) Stability of apo, binary (protein:nucleotide), and ternary (protein:nucleotide:pseudosubstrate) states of wtPKA and Y204A mutant as seen by differentialscanning fluorimetry.

Proc Natl Acad Sci U S A 2017 Feb 7;114(6):E931-E940. PMID: 28115705 PMCID: PMC5307475

Figure 4. Phosphatase assays and time course measurements on PTP10D a. Michealis-Menten kinetics for the phosphatase activity of PTP10D and the F76L mutant with various substrates. b. Time course measurements to ascertain the life time of the phosphatase reaction as catalyzed by PTP10D and the F76L mutant.

Biochemistry 2011 Nov 22;50(46):10114-25. PMID: 22007620 PMCID: PMC3667199

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