2MHS

NMR Structure of human Mcl-1

2MHS の概要

• エントリーDOI: 10.2210/pdb2mhs/pdb
• NMR情報: BMRB: 19654
• 分子名称: Induced myeloid leukemia cell differentiation protein Mcl-1 (1 entity in total)
• 機能のキーワード: mcl-1, bcl-2 family, bh domain, apoptosis, cancer drug, gft nmr
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass membrane protein (Potential): Q07820
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18866.35

構造登録者

Liu, G.,Poppe, L.,Aoki, K.,Yamane, H.,Lewis, J.,Szyperski, T. (登録日: 2013-12-04, 公開日: 2014-05-14, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

SOLUTION NMR