4WGI

A Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1)

Summary for 4WGI

• Entry DOI: 10.2210/pdb4wgi/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose-binding periplasmic protein,Induced myeloid leukemia cell differentiation protein Mcl-1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, (2S)-2-[(2S,3R)-10-{[(4-fluorophenyl)sulfonyl]amino}-3-methyl-2-[(methyl{[4-(trifluoromethyl)phenyl]carbamoyl}amino)methyl]-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-5(6H)-yl]propanoic acid, ... (6 entities in total)
• Functional Keywords: fusion protein, mbp, transport protein, transport protein-inhibitor complex, apoptosis-inhibitor complex, apoptosis/inhibitor
• Biological source: Escherichia coli O157:H7; More
• Total number of polymer chains: 1
• Total formula weight: 58804.38

Authors

Clifton, M.C.,Fairman, J.W.,Fang, C.,D'Souza, B.,Fulroth, B.,Leed, A.,McCarren, P.,Wang, L.,Wang, Y.,Kaushik, V.,Palmer, M.,Wei, G.,Golub, T.R.,Hubbard, B.K.,Serrano-Wu, M.H. (deposition date: 2014-09-18, release date: 2014-11-19, Last modification date: 2023-09-27)

Primary citation

Fang, C.,D'Souza, B.,Thompson, C.F.,Clifton, M.C.,Fairman, J.W.,Fulroth, B.,Leed, A.,McCarren, P.,Wang, L.,Wang, Y.,Feau, C.,Kaushik, V.K.,Palmer, M.,Wei, G.,Golub, T.R.,Hubbard, B.K.,Serrano-Wu, M.H.
Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1).
Acs Med.Chem.Lett., 5:1308-1312, 2014

PubMed Abstract: A direct binding screen of 100 000 sp(3)-rich molecules identified a single diastereomer of a macrolactam core that binds specifically to myeloid cell leukemia 1 (MCL1). A comprehensive toolbox of biophysical methods was applied to validate the original hit and subsequent analogues and also established a binding mode competitive with NOXA BH3 peptide. X-ray crystallography of ligand bound to MCL1 reveals a remarkable ligand/protein shape complementarity that diverges from previously disclosed MCL1 inhibitor costructures.

PubMed: 25516789
DOI: 10.1021/ml500388q

Experimental method

X-RAY DIFFRACTION (1.85 Å)