4UMR

Structure of MELK in complex with inhibitors

Summary for 4UMR

• Entry DOI: 10.2210/pdb4umr/pdb
• Related: 4D2T 4D2V 4D2W 4UMP 4UMQ 4UMT 4UMU
• Descriptor: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE, 4-fluoro-N-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (3 entities in total)
• Functional Keywords: transferase, fragment based drug design
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell membrane ; Peripheral membrane protein : Q14680
• Total number of polymer chains: 1
• Total formula weight: 41162.58

Authors

Johnson, C.N.,Berdini, V.,Beke, L.,Bonnet, P.,Brehmer, D.,Coyle, J.E.,Day, P.J.,Frederickson, M.,Freyne, E.J.E.,Gilissen, R.A.H.J.,Hamlett, C.C.F.,Howard, S.,Meerpoel, L.,McMenamin, R.,Patel, S.,Rees, D.C.,Sharff, A.,Sommen, F.,Wu, T.,Linders, J.T.M. (deposition date: 2014-05-20, release date: 2014-10-08, Last modification date: 2024-05-08)

Primary citation

Johnson, C.N.,Berdini, V.,Beke, L.,Bonnet, P.,Brehmer, D.,Coyle, J.E.,Day, P.J.,Frederickson, M.,Freyne, E.J.E.,Gilissen, R.A.H.J.,Hamlett, C.C.F.,Howard, S.,Meerpoel, L.,Mcmenamin, R.,Patel, S.,Rees, D.C.,Sharff, A.,Sommen, F.,Wu, T.,Linders, J.T.M.
Fragment-Based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase
Acs Med.Chem.Lett., 6:25-, 2015

PubMed Abstract: Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.

PubMed: 25589925
DOI: 10.1021/ML5001245

Experimental method

X-RAY DIFFRACTION (3 Å)