PDBsum entry 4wms

Apoptosis

PDB id: 4wms

Contents

Protein chain

511 a.a.

Ligands

GLC-GLC

EDO ×2

FMT ×10

Metals

_MG

Waters ×425

PDB id:

4wms

Name:

Apoptosis

Title:

Structure of apo mbp-mcl1 at 1.9a

Structure:

Mbp-mcl1 chimera protein. Chain: a. Fragment: unp p0aex9 residues 27-392,unp q07820 residues 174-321. Engineered: yes. Mutation: yes

Source:

Escherichia coli, homo sapiens. Human. Organism_taxid: 83333, 9606. Strain: k12. Gene: male, b4034, jw3994, mcl1, bcl2l3. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.176 R-free: 0.214

Authors:

M.C.Clifton,D.M.Dranow

Key ref:

M.C.Clifton et al. (2015). A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1. Plos One, 10, e0125010. PubMed id: 25909780 DOI: 10.1371/journal.pone.0125010

Date:

09-Oct-14 Release date: 06-May-15

Protein chain

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 511 a.a.*

Protein chain

Q07820  (MCL1_HUMAN) -  Induced myeloid leukemia cell differentiation protein Mcl-1 from Homo sapiens

Seq: 350 a.a.

Struc: 511 a.a.*

* PDB and UniProt seqs differ at 165 residue positions (black crosses)

DOI no: 10.1371/journal.pone.0125010

Plos One 10:e0125010 (2015)

PubMed id: 25909780

A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.

M.C.Clifton, D.M.Dranow, A.Leed, B.Fulroth, J.W.Fairman, J.Abendroth, K.A.Atkins, E.Wallace, D.Fan, G.Xu, Z.J.Ni, D.Daniels, J.Van Drie, G.Wei, A.B.Burgin, T.R.Golub, B.K.Hubbard, M.H.Serrano-Wu.

ABSTRACT

Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.