4L59

Crystal structure of the 3-MBT repeat domain of L3MBTL3 and UNC2533 complex

Summary for 4L59

• Entry DOI: 10.2210/pdb4l59/pdb
• Descriptor: Lethal(3)malignant brain tumor-like protein 3, 4-(pyrrolidin-1-yl)-1-{4-[2-(pyrrolidin-1-yl)ethyl]phenyl}piperidine, SULFATE ION, ... (5 entities in total)
• Functional Keywords: 3-mbt repeat domain, l3mbtl3, unc2533, structural genomics, structural genomics consortium, sgc, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q96JM7
• Total number of polymer chains: 1
• Total formula weight: 37073.20

Authors

Zhong, N.,Dong, A.,Ravichandran, M.,Camerino, M.A.,Dickson, B.M.,James, L.I.,Baughman, B.M.,Norris, J.L.,Kireev, D.B.,Janzen, W.P.,Graslund, S.,Frye, S.V.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Brown, P.J.,Structural Genomics Consortium (SGC) (deposition date: 2013-06-10, release date: 2013-07-10, Last modification date: 2023-09-20)

Primary citation

Camerino, M.A.,Zhong, N.,Dong, A.,Dickson, B.M.,James, L.I.,Baughman, B.M.,Norris, J.L.,Kireev, D.B.,Janzen, W.P.,Arrowsmith, C.H.,Frye, S.V.
The structure-activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface.
Medchemcomm, 4:1501-1507, 2013

PubMed Abstract: We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding.

PubMed: 24466405
DOI: 10.1039/C3MD00197K

Experimental method

X-RAY DIFFRACTION (2.29 Å)