7SWG

cTnC-TnI chimera complexed with A1

Summary for 7SWG

• Entry DOI: 10.2210/pdb7swg/pdb
• NMR Information: BMRB: 30965
• Descriptor: Troponin C, slow skeletal and cardiac muscles,Troponin I, cardiac muscle chimera, 4-(3-cyano-3-methylazetidine-1-carbonyl)-N-[(3S)-7-fluoro-6-methyl-3,4-dihydro-2H-1-benzopyran-3-yl]-5-methyl-1H-pyrrole-2-sulfonamide (2 entities in total)
• Functional Keywords: cardiac troponin, calcium sensitizer, metal binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 14668.62

Authors

Poppe, L.,Hartman, J.J.,Romero, A.,Reagan, J.D. (deposition date: 2021-11-19, release date: 2022-04-06, Last modification date: 2024-05-15)

Primary citation

Poppe, L.,Hartman, J.J.,Romero, A.,Reagan, J.D.
Structural and Thermodynamic Model for the Activation of Cardiac Troponin.
Biochemistry, 61:741-748, 2022

PubMed Abstract: Cardiac troponin is a regulatory protein complex located on the sarcomere that regulates the engagement of myosin on actin filaments. Low-molecular weight modulators of troponin that bind allosterically with the calcium ion have the potential to improve cardiac contractility in patients with reduced cardiac function. Here we propose an approach to the rational design of troponin modulators through the combined use of solution nuclear magnetic resonance and isothermal titration calorimetry methods. In contrast to traditional approaches limited to calcium and activator-bound troponin structures, here we analyzed the structural and thermodynamic impact of an activator in the context of the troponin functional cycle. This led us to propose a rationale for developing an efficacious troponin activator.

PubMed: 35349258
DOI: 10.1021/acs.biochem.2c00084

Experimental method

SOLUTION NMR