2MHS

NMR Structure of human Mcl-1

Summary for 2MHS

• Entry DOI: 10.2210/pdb2mhs/pdb
• NMR Information: BMRB: 19654
• Descriptor: Induced myeloid leukemia cell differentiation protein Mcl-1 (1 entity in total)
• Functional Keywords: mcl-1, bcl-2 family, bh domain, apoptosis, cancer drug, gft nmr
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass membrane protein (Potential): Q07820
• Total number of polymer chains: 1
• Total formula weight: 18866.35

Authors

Liu, G.,Poppe, L.,Aoki, K.,Yamane, H.,Lewis, J.,Szyperski, T. (deposition date: 2013-12-04, release date: 2014-05-14, Last modification date: 2024-05-15)

Primary citation

Liu, G.,Poppe, L.,Aoki, K.,Yamane, H.,Lewis, J.,Szyperski, T.
High-Quality NMR Structure of Human Anti-Apoptotic Protein Domain Mcl-1(171-327) for Cancer Drug Design.
Plos One, 9:e96521-e96521, 2014

PubMed Abstract: A high-quality NMR solution structure is presented for protein hMcl-1(171-327) which comprises residues 171-327 of the human anti-apoptotic protein Mcl-1 (hMcl-1). Since this construct contains the three Bcl-2 homology (BH) sequence motifs which participate in forming a binding site for inhibitors of hMcl-1, it is deemed to be crucial for structure-based design of novel anti-cancer drugs blocking the Mcl1 related anti-apoptotic pathway. While the coordinates of an NMR solution structure for a corresponding construct of the mouse homologue (mMcl-1) are publicly available, our structure is the first atomic resolution structure reported for the 'apo form' of the human protein. Comparison of the two structures reveals that hMcl-1(171-327) exhibits a somewhat wider ligand/inhibitor binding groove as well as a different charge distribution within the BH3 binding groove. These findings strongly suggest that the availability of the human structure is of critical importance to support future design of cancer drugs.

PubMed: 24789074
DOI: 10.1371/journal.pone.0096521

Experimental method

SOLUTION NMR