6MBE
Human Mcl-1 in complex with the designed peptide dM7
Summary for 6MBE
| Entry DOI | 10.2210/pdb6mbe/pdb |
| Descriptor | Induced myeloid leukemia cell differentiation protein Mcl-1, dM7, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | anti-apoptotic bcl-2, inhibitor, design, apoptosis |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 20227.50 |
| Authors | Jenson, J.M.,Keating, A.E. (deposition date: 2018-08-29, release date: 2019-03-06, Last modification date: 2023-10-11) |
| Primary citation | Frappier, V.,Jenson, J.M.,Zhou, J.,Grigoryan, G.,Keating, A.E. Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1. Structure, 27:606-617.e5, 2019 Cited by PubMed Abstract: Understanding the relationship between protein sequence and structure well enough to design new proteins with desired functions is a longstanding goal in protein science. Here, we show that recurring tertiary structural motifs (TERMs) in the PDB provide rich information for protein-peptide interaction prediction and design. TERM statistics can be used to predict peptide binding energies for Bcl-2 family proteins as accurately as widely used structure-based tools. Furthermore, design using TERM energies (dTERMen) rapidly and reliably generates high-affinity peptide binders of anti-apoptotic proteins Bfl-1 and Mcl-1 with just 15%-38% sequence identity to any known native Bcl-2 family protein ligand. High-resolution structures of four designed peptides bound to their targets provide opportunities to analyze the strengths and limitations of the computational design method. Our results support dTERMen as a powerful approach that can complement existing tools for protein engineering. PubMed: 30773399DOI: 10.1016/j.str.2019.01.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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