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PDBsum entry 1oyx

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protein ligands Protein-protein interface(s) links
Transcription PDB id
1oyx
Jmol
Contents
Protein chains
313 a.a. *
Ligands
SO4 ×14
MES ×7
Waters ×507
* Residue conservation analysis
PDB id:
1oyx
Name: Transcription
Title: Crystal structure of 3-mbt repeats of lethal (3) malignant brain tumor (seleno-met) at 1.85 angstrom
Structure: Lethal(3)malignant brain tumor-like protein. Chain: a, b, c. Fragment: residues 197-527. Synonym: l3, mbt-like, l3, mbt protein homolog, h-l3, mbt protein, h-l3, mbt. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: brain. Gene: l3mbtl or l3mbt or kiaa0681. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.85Å     R-factor:   0.209     R-free:   0.238
Authors: W.K.Wang,V.Tereshko,P.Boccuni,D.Macgrogan,S.D.Nimer, D.J.Patel
Key ref:
W.K.Wang et al. (2003). Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets. Structure, 11, 775-789. PubMed id: 12842041 DOI: 10.1016/S0969-2126(03)00127-8
Date:
07-Apr-03     Release date:   19-Aug-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9Y468  (LMBL1_HUMAN) -  Lethal(3)malignant brain tumor-like protein 1
Seq:
Struc:
 
Seq:
Struc:
752 a.a.
313 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 

 

 
DOI no: 10.1016/S0969-2126(03)00127-8 Structure 11:775-789 (2003)
PubMed id: 12842041  
 
 
Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets.
W.K.Wang, V.Tereshko, P.Boccuni, D.MacGrogan, S.D.Nimer, D.J.Patel.
 
  ABSTRACT  
 
We report on the X-ray structure of three 100-amino acid mbt repeats in h-l(3)mbt, a polycomb group protein involved in transcriptional repression, whose gene is located in a region of chromosome 20 associated with hematopoietic malignancies. Interdigitation between the extended arms and cores of the mbt repeats results in a three-leaved propeller-like architecture, containing a central cavity. We have identified one ligand binding pocket per mbt repeat, which accommodates either the morphilino ring of MES or the proline ring of the C-terminal peptide segment, within a cavity lined by aromatic amino acids. Strikingly, phenotypic alterations resulting from point mutations or deletions in the mbt repeats of the related Drosophila SCM protein are clustered in and around the ligand binding pocket.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. MES Ligand Binding Pockets in Trigonal 3mbt Structures(A) Superimposition of three mbt repeats with bound MES molecules in the seleno-met structure. A MES molecule (labeled 1, 2, and 3) is bound to each b subunit core (colored as in Figure 2A).(B) The mutation sites are located in and around the MES binding pocket (second mbt repeat) in the 3mbt structure (seleno-met). The morphilino ring of the bound MES molecule (red) is encapsulated by polar and aromatic residues (silver). The electron density for bound MES is shown in a chicken wire representation. Residues that are point mutated (magenta) and deleted (blue) are highlighted with the letters M and D, respectively. Residue M357 in the second repeat is included, since it occupies a position analogous to R461 in the third repeat (see [C] and [D]). Hydrogen bond networks are indicated by dotted lines (magenta). Oxygen and nitrogen atoms are colored red and blue, respectively.(C) The surface representation of the open form of the MES (yellow) binding pocket from the third mbt repeat in the seleno-met structure. Residues lining this pocket are indicated in black. Arginine R461 is indicated in dotted surface (pink) representation with its side chain in a stick mode (white). Conserved residues among mbt repeats that are mutated in the SCM protein (Bornemann et al., 1998) are explicitly indicated in blue (deletion mutations, labeled D) and red (point mutations, labeled M).(D) The surface representation of the closed form of the MES binding pocket from the third mbt repeat in the GTP-containing native 1 structure. The R461 arginine finger flips its long and bulky side chain into the pocket, closing this site to MES ligands. This alignment is stabilized by a single hydrogen bond with residue D459 (point mutated in mbt of SCM protein; Bornemann et al., 1998).
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 775-789) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
19494831 C.Grimm, R.Matos, N.Ly-Hartig, U.Steuerwald, D.Lindner, V.Rybin, J.Müller, and C.W.Müller (2009).
Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt.
  EMBO J, 28, 1965-1977.
PDB code: 3h6z
19233876 Y.Guo, N.Nady, C.Qi, A.Allali-Hassani, H.Zhu, P.Pan, M.A.Adams-Cioaba, M.F.Amaya, A.Dong, M.Vedadi, M.Schapira, R.J.Read, C.H.Arrowsmith, and J.Min (2009).
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
  Nucleic Acids Res, 37, 2204-2210.
PDB codes: 3cey 3f70
18408754 N.Kalakonda, W.Fischle, P.Boccuni, N.Gurvich, R.Hoya-Arias, X.Zhao, Y.Miyata, D.Macgrogan, J.Zhang, J.K.Sims, J.C.Rice, and S.D.Nimer (2008).
Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1.
  Oncogene, 27, 4293-4304.  
17932512 C.Grimm, A.G.de Ayala Alonso, V.Rybin, U.Steuerwald, N.Ly-Hartig, W.Fischle, J.Müller, and C.W.Müller (2007).
Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein Sex comb on midleg.
  EMBO Rep, 8, 1031-1037.
PDB codes: 2r57 2r58 2r5a 2r5m
17988933 G.Kustatscher, and A.G.Ladurner (2007).
Modular paths to 'decoding' and 'wiping' histone lysine methylation.
  Curr Opin Chem Biol, 11, 628-635.  
18042461 H.Li, W.Fischle, W.Wang, E.M.Duncan, L.Liang, S.Murakami-Ishibe, C.D.Allis, and D.J.Patel (2007).
Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger.
  Mol Cell, 28, 677-691.
PDB codes: 2rhi 2rhu 2rhx 2rhy 2rhz 2ri2 2ri3 2ri5 2ri7
18026117 J.Min, A.Allali-Hassani, N.Nady, C.Qi, H.Ouyang, Y.Liu, F.MacKenzie, M.Vedadi, and C.H.Arrowsmith (2007).
L3MBTL1 recognition of mono- and dimethylated histones.
  Nat Struct Mol Biol, 14, 1229-1230.
PDB codes: 2pqw 2rjc 2rjd 2rje 2rjf
17409073 M.M.Harrison, X.Lu, and H.R.Horvitz (2007).
LIN-61, one of two Caenorhabditis elegans malignant-brain-tumor-repeat-containing proteins, acts with the DRM and NuRD-like protein complexes in vulval development but not in certain other biological processes.
  Genetics, 176, 255-271.  
17540172 P.Trojer, G.Li, R.J.Sims, A.Vaquero, N.Kalakonda, P.Boccuni, D.Lee, H.Erdjument-Bromage, P.Tempst, S.D.Nimer, Y.H.Wang, and D.Reinberg (2007).
L3MBTL1, a histone-methylation-dependent chromatin lock.
  Cell, 129, 915-928.  
17984965 S.D.Taverna, H.Li, A.J.Ruthenburg, C.D.Allis, and D.J.Patel (2007).
How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.
  Nat Struct Mol Biol, 14, 1025-1040.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17599839 S.Wu, R.C.Trievel, and J.C.Rice (2007).
Human SFMBT is a transcriptional repressor protein that selectively binds the N-terminal tail of histone H3.
  FEBS Lett, 581, 3289-3296.  
16618800 T.Klymenko, B.Papp, W.Fischle, T.Köcher, M.Schelder, C.Fritsch, B.Wild, M.Wilm, and J.Müller (2006).
A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities.
  Genes Dev, 20, 1110-1122.  
15689505 N.Nameki, N.Tochio, S.Koshiba, M.Inoue, T.Yabuki, M.Aoki, E.Seki, T.Matsuda, Y.Fujikura, M.Saito, M.Ikari, M.Watanabe, T.Terada, M.Shirouzu, M.Yoshida, H.Hirota, A.Tanaka, Y.Hayashizaki, P.Güntert, T.Kigawa, and S.Yokoyama (2005).
Solution structure of the PWWP domain of the hepatoma-derived growth factor family.
  Protein Sci, 14, 756-764.
PDB code: 1n27
15964847 P.R.Nielsen, D.Nietlispach, A.Buscaino, R.J.Warner, A.Akhtar, A.G.Murzin, N.V.Murzina, and E.D.Laue (2005).
Structure of the chromo barrel domain from the MOF acetyltransferase.
  J Biol Chem, 280, 32326-32331.
PDB code: 2bud
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.