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Fig. 2 | Algorithms for Molecular Biology

Fig. 2

From: Precise parallel volumetric comparison of molecular surfaces and electrostatic isopotentials

Fig. 2

Steric hindrance in the tyrosine kinase active site induced by a large gatekeeper residue. A transparent cross section of the c-Kit tyrosine kinase is shown in gray (pdb: 1t46). The inhibitor imatinib (magenta sticks) is co-crystallized with c-Kit in the active site (dark gray channel). Interleukin-2 tyrosine kinase (pdb: 1snx) is structurally aligned to the c-Kit kinase but not shown for clarity, except for its gatekeeper residue F435 (cyan spheres). This phenylalanine gatekeeper residue is substantially larger than the threonine gatekeeper of c-Kit, creating steric hindrance that prevents longer inhibitors like imatinib from binding in Interleukin-2. Identifying substitutions that influence binding preferences through steric hindrance is one important application of CSG-based comparison methods like pClay

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