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PDBsum entry 1nk2
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protein dna_rna links
DNA binding protein/DNA PDB id
1nk2

 

 

 

 

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Contents
Protein chain
77 a.a. *
DNA/RNA
* Residue conservation analysis
PDB id:
1nk2
Name: DNA binding protein/DNA
Title: Vnd/nk-2 homeodomain/DNA complex, nmr, 20 structures
Structure: DNA (5'-d( Tp Gp Tp Gp Tp Cp Ap Ap Gp Tp Gp Gp Cp Tp Gp T)- 3'). Chain: a. Engineered: yes. DNA (5'-d( Ap Cp Ap Gp Cp Cp Ap Cp Tp Tp Gp Ap Cp Ap Cp A)- 3'). Chain: b. Engineered: yes. Homeobox protein vnd.
Source: Synthetic: yes. Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Organ: fruit. Gene: potential. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: J.M.Gruschus,D.H.H.Tsao,L.-H.Wang,M.Nirenberg,J.A.Ferretti
Key ref:
J.M.Gruschus et al. (1997). Interactions of the vnd/NK-2 homeodomain with DNA by nuclear magnetic resonance spectroscopy: basis of binding specificity. Biochemistry, 36, 5372-5380. PubMed id: 9154919 DOI: 10.1021/bi9620060
Date:
06-May-98     Release date:   23-Feb-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22808  (VND_DROME) -  Homeobox protein vnd from Drosophila melanogaster
Seq:
Struc: 		 
Seq:
Struc: 		723 a.a.
77 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains
  T-G-T-G-T-C-A-A-G-T-G-G-C-T-G-T 16 bases
  A-C-A-G-C-C-A-C-T-T-G-A-C-A-C-A 16 bases

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1021/bi9620060 Biochemistry 36:5372-5380 (1997)
PubMed id: 9154919  
 
 
Interactions of the vnd/NK-2 homeodomain with DNA by nuclear magnetic resonance spectroscopy: basis of binding specificity.
J.M.Gruschus, D.H.Tsao, L.H.Wang, M.Nirenberg, J.A.Ferretti.
 
  ABSTRACT  
 
The interactions responsible for the nucleotide sequence-specific binding of the vnd/NK-2 homeodomain of Drosophila melanogaster to its consensus DNA binding site have been identified. A three-dimensional structure of the vnd/NK-2 homeodomain-DNA complex is presented, with emphasis on the structure of regions of observed protein-DNA contacts. This structure is based on protein-DNA distance restraints derived from NMR data, along with homology modeling, solvated molecular dynamics, and results from methylation and ethylation interference experiments. Helix III of the homeodomain binds in the major groove of the DNA and the N-terminal arm binds in the minor groove, in analogy with other homeodomain-DNA complexes whose structures have been reported. The vnd/NK-2 homeodomain recognizes the unusual DNA consensus sequence 5'-CAAGTG-3'. The roles in sequence specificity and strength of binding of individual amino acid residues that make contact with the DNA are described. We show, based primarily on the observed protein-DNA contacts, that the interaction of Y54 with the DNA is the major determinant of this uncommon nucleotide binding specificity in the vnd/NK-2 homeodomain-DNA complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21078959 D.Vuzman, and Y.Levy (2010).
DNA search efficiency is modulated by charge composition and distribution in the intrinsically disordered tail.
  Proc Natl Acad Sci U S A, 107, 21004-21009.  
19336474 A.Carré, G.Szinnai, M.Castanet, S.Sura-Trueba, E.Tron, I.Broutin-L'Hermite, P.Barat, C.Goizet, D.Lacombe, M.L.Moutard, C.Raybaud, C.Raynaud-Ravni, S.Romana, H.Ythier, J.Léger, and M.Polak (2009).
Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case.
  Hum Mol Genet, 18, 2266-2276.  
19780584 J.H.Ju, J.S.Maeng, D.Y.Lee, G.Piszczek, E.P.Gelmann, and J.M.Gruschus (2009).
Interactions of the acidic domain and SRF interacting motifs with the NKX3.1 homeodomain.
  Biochemistry, 48, 10601-10607.  
19795518 T.Von Ohlen, C.Moses, and W.Poulson (2009).
Ind represses msh expression in the intermediate column of the Drosophila neuroectoderm, through direct interaction with upstream regulatory DNA.
  Dev Dyn, 238, 2735-2744.  
18557759 C.Abate-Shen, M.M.Shen, and E.Gelmann (2008).
Integrating differentiation and cancer: the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis.
  Differentiation, 76, 717-727.  
18585360 M.B.Noyes, R.G.Christensen, A.Wakabayashi, G.D.Stormo, M.H.Brodsky, and S.A.Wolfe (2008).
Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites.
  Cell, 133, 1277-1289.  
17729273 P.Del Vecchio, P.Carullo, G.Barone, B.Pagano, G.Graziano, A.Iannetti, R.Acquaviva, A.Leonardi, and S.Formisano (2008).
Conformational stability and DNA binding energetics of the rat thyroid transcription factor 1 homeodomain.
  Proteins, 70, 748-760.  
18411210 S.Keleş, C.L.Warren, C.D.Carlson, and A.Z.Ansari (2008).
CSI-Tree: a regression tree approach for modeling binding properties of DNA-binding molecules based on cognate site identification (CSI) data.
  Nucleic Acids Res, 36, 3171-3184.  
16920361 C.Crane-Robinson, A.I.Dragan, and P.L.Privalov (2006).
The extended arms of DNA-binding domains: a tale of tails.
  Trends Biochem Sci, 31, 547-552.  
16460268 K.L.Clark, K.E.Yutzey, and D.W.Benson (2006).
Transcription factors and congenital heart defects.
  Annu Rev Physiol, 68, 97.  
15741164 H.Sellak, C.Choi, N.Browner, and T.M.Lincoln (2005).
Upstream stimulatory factors (USF-1/USF-2) regulate human cGMP-dependent protein kinase I gene expression in vascular smooth muscle cells.
  J Biol Chem, 280, 18425-18433.  
15870192 L.H.Wang, R.Chmelik, D.Tang, and M.Nirenberg (2005).
Identification and analysis of vnd/NK-2 homeodomain binding sites in genomic DNA.
  Proc Natl Acad Sci U S A, 102, 7097-7102.  
15731308 H.DU, and H.S.Taylor (2004).
Molecular regulation of mullerian development by Hox genes.
  Ann N Y Acad Sci, 1034, 152-165.  
12850523 E.P.Gelmann (2003).
Searching for the gatekeeper oncogene of prostate cancer.
  Crit Rev Oncol Hematol, 46, S11-S20.  
14580198 K.J.Hwang, B.Xiang, J.M.Gruschus, K.Y.Nam, K.T.No, M.Nirenberg, and J.A.Ferretti (2003).
Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound to DNA induced by an embryonically lethal A35T point mutation.
  Biochemistry, 42, 12522-12531.
PDB code: 1qry
12626758 K.Koizumi, C.Lintas, M.Nirenberg, J.S.Maeng, J.H.Ju, J.W.Mack, J.M.Gruschus, W.F.Odenwald, and J.A.Ferretti (2003).
Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure.
  Proc Natl Acad Sci U S A, 100, 3119-3124.  
12548619 W.Flader, B.Wellenzohn, R.H.Winger, A.Hallbrucker, E.Mayer, and K.R.Liedl (2003).
Stepwise induced fit in the pico- to nanosecond time scale governs the complexation of the even-skipped transcriptional repressor homeodomain to DNA.
  Biopolymers, 68, 139-149.  
  11854319 H.Krude, B.Schütz, H.Biebermann, A.von Moers, D.Schnabel, H.Neitzel, H.Tönnies, D.Weise, A.Lafferty, S.Schwarz, M.DeFelice, A.von Deimling, F.van Landeghem, R.DiLauro, and A.Grüters (2002).
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency.
  J Clin Invest, 109, 475-480.  
12232052 L.H.Wang, R.Chmelik, and M.Nirenberg (2002).
Sequence-specific DNA binding by the vnd/NK-2 homeodomain of Drosophila.
  Proc Natl Acad Sci U S A, 99, 12721-12726.  
  12186638 S.Banerjee-Basu, and A.D.Baxevanis (2002).
The DNA-binding region of RAG 1 is not a homeodomain.
  Genome Biol, 3, INTERACTIONS1004.  
11391564 G.Iurcu-Mustata, D.Van Belle, R.Wintjens, M.Prévost, and M.Rooman (2001).
Role of salt bridges in homeodomains investigated by structural analyses and molecular dynamics simulations.
  Biopolymers, 59, 145-159.  
11470884 S.Banerjee-Basu, and A.D.Baxevanis (2001).
Molecular evolution of the homeodomain family of transcription factors.
  Nucleic Acids Res, 29, 3258-3269.  
11125116 S.Banerjee-Basu, D.W.Sink, and A.D.Baxevanis (2001).
The Homeodomain Resource: sequences, structures, DNA binding sites and genomic information.
  Nucleic Acids Res, 29, 291-293.  
10903346 H.Kasahara, B.Lee, J.J.Schott, D.W.Benson, J.G.Seidman, C.E.Seidman, and S.Izumo (2000).
Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease.
  J Clin Invest, 106, 299-308.  
10889025 R.A.Grant, M.A.Rould, J.D.Klemm, and C.O.Pabo (2000).
Exploring the role of glutamine 50 in the homeodomain-DNA interface: crystal structure of engrailed (Gln50 --> ala) complex at 2.0 A.
  Biochemistry, 39, 8187-8192.
PDB code: 1du0
10799563 R.G.Mirmira, H.Watada, and M.S.German (2000).
Beta-cell differentiation factor Nkx6.1 contains distinct DNA binding interference and transcriptional repression domains.
  J Biol Chem, 275, 14743-14751.  
10592263 S.Banerjee-Basu, J.F.Ryan, and A.D.Baxevanis (2000).
The homeodomain resource: a prototype database for a large protein family.
  Nucleic Acids Res, 28, 329-330.  
11003663 V.Dave, C.Zhao, F.Yang, C.S.Tung, and J.Ma (2000).
Reprogrammable recognition codes in bicoid homeodomain-DNA interaction.
  Mol Cell Biol, 20, 7673-7684.  
9990841 G.La Penna, M.Mormino, F.Pioli, A.Perico, R.Fioravanti, J.M.Gruschus, and J.A.Ferretti (1999).
Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: first-order mode-coupling approximation.
  Biopolymers, 49, 235-254.  
9988700 L.Perrone, G.Tell, and R.Di Lauro (1999).
Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain.
  J Biol Chem, 274, 4640-4645.  
10336376 R.Schleif (1999).
Arm-domain interactions in proteins: a review.
  Proteins, 34, 1-3.  
10502778 S.Banerjee-Basu, and A.D.Baxevanis (1999).
Threading analysis of the Pitx2 homeodomain: predicted structural effects of mutations causing Rieger syndrome and iridogoniodysgenesis.
  Hum Mutat, 14, 312-319.  
9636163 B.Xiang, S.Weiler, M.Nirenberg, and J.A.Ferretti (1998).
Structural basis of an embryonically lethal single Ala --> Thr mutation in the vnd/NK-2 homeodomain.
  Proc Natl Acad Sci U S A, 95, 7412-7416.  
  9832510 J.B.Weiss, T.Von Ohlen, D.M.Mellerick, G.Dressler, C.Q.Doe, and M.P.Scott (1998).
Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity.
  Genes Dev, 12, 3591-3602.  
9699631 S.A.Dames, R.A.Kammerer, R.Wiltscheck, J.Engel, and A.T.Alexandrescu (1998).
NMR structure of a parallel homotrimeric coiled coil.
  Nat Struct Biol, 5, 687-691.
PDB code: 1aq5
9556579 S.Weiler, J.M.Gruschus, D.H.Tsao, L.Yu, L.H.Wang, M.Nirenberg, and J.A.Ferretti (1998).
Site-directed mutations in the vnd/NK-2 homeodomain. Basis of variations in structure and sequence-specific DNA binding.
  J Biol Chem, 273, 10994-11000.  
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.

 

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