PDBsum entry 1yqr

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protein dna_rna metals links
Hydrolase/DNA PDB id
Protein chain
314 a.a. *
_CA ×2
Waters ×129
* Residue conservation analysis
PDB id:
Name: Hydrolase/DNA
Title: Catalytically inactive human 8-oxoguanine glycosylase crosslinked to oxog containing DNA
Structure: 5'-d(p Gp Gp Tp Ap Gp Ap Cp Cp Tp Gp Gp Ap Cp G)- 3'. Chain: b. Engineered: yes. 5'-d(p Cp Gp Tp Cp Cp Ap (8Og) p Gp Tp Cp Tp Ap Cp C)-3'. Chain: c. Engineered: yes. N-glycosylase/DNA lyase.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: ogg1, mmh, mutm, ogh1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Trimer (from PQS)
2.43Å     R-factor:   0.219     R-free:   0.251
Authors: A.Banerjee,W.Yang,M.Karplus,G.L.Verdine
Key ref:
A.Banerjee et al. (2005). Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA. Nature, 434, 612-618. PubMed id: 15800616 DOI: 10.1038/nature03458
02-Feb-05     Release date:   05-Apr-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O15527  (OGG1_HUMAN) -  N-glycosylase/DNA lyase
345 a.a.
314 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - DNA-(apurinic or apyrimidinic site) lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   5 terms 
  Biological process     metabolic process   21 terms 
  Biochemical function     catalytic activity     12 terms  


DOI no: 10.1038/nature03458 Nature 434:612-618 (2005)
PubMed id: 15800616  
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA.
A.Banerjee, W.Yang, M.Karplus, G.L.Verdine.
How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G). Here we report the use of a covalent trapping strategy to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1), in the act of interrogating normal DNA. The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site.
  Selected figure(s)  
Figure 1.
Figure 1: Generation of 8-oxoguanine (oxoG), its recognition by human 8-oxoguanine DNA glycosylase (hOGG1) and overview of the structure-based trapping strategy used here to obtain a complex of hOGG1 bound to undamaged DNA. a, Structural differences between G and oxoG. Inset: close-up view of the lesion recognition pocket of hOGG1 showing residues involved in recognition of oxoG and catalysis, highlighting the direct contact between N7 H and Gly 42, and the catalytic nucleophile Lys 249. b, Schematic overview of the crosslinking and validation strategy. c, Details of the trapping chemistry. Attachment of a tether at the N4 position of cytosine is known to preserve Watson -Crick pairing in protein-unbound DNA, with the tether protruding into the major groove^31. d, Sequence of the DNA duplex used in this work.
Figure 5.
Figure 5: Superposition of the oxoG complex with the G complex in the region around the protein -DNA interface. a, Overlay using the protein backbone only (grey) for superposition, with the DNA backbone of the oxoG complex in green and G complex in gold. Spheres indicate Ca^2+ ions. Residues that interact with DNA through backbone amide nitrogen atoms are denoted in magenta, whereas those that interact through side chains are in black. Dotted lines indicate hydrogen bonds. b, Ribbon diagram in the same orientation as a, but showing the whole DNA duplex. c, Comparison of the DNA in the two complexes, using the left flank for superposition. Arrows labelled a, b and c indicate bonds that have undergone significant rotations: +110 for a (C4' -C5' bond of the residue 3' to oxoG/G), +119 for b (C4' -C5' bond of oxoG/G) and -151 for c (P -O5' bond of oxoG/G).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2005, 434, 612-618) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22659876 C.Yi, B.Chen, B.Qi, W.Zhang, G.Jia, L.Zhang, C.J.Li, A.R.Dinner, C.G.Yang, and C.He (2012).
Duplex interrogation by a direct DNA repair protein in search of base damage.
  Nat Struct Mol Biol, 19, 671-676.
PDB codes: 3rzg 3rzh 3rzj 3rzk 3rzl 3rzm 3s57 3s5a
21267490 A.Ebrahimi, M.Habibi-Khorassani, and S.Bazzi (2011).
The impact of protonation and deprotonation of 3-methyl-2'-deoxyadenosine on N-glycosidic bond cleavage.
  Phys Chem Chem Phys, 13, 3334-3343.  
21220122 B.Dalhus, M.Forsbring, I.H.Helle, E.S.Vik, R.J.Forstrøm, P.H.Backe, I.Alseth, and M.Bjørås (2011).
Separation-of-function mutants unravel the dual-reaction mode of human 8-oxoguanine DNA glycosylase.
  Structure, 19, 117-127.
PDB code: 2xhi
20876689 E.Fadda, and R.Pomès (2011).
On the molecular basis of uracil recognition in DNA: comparative study of T-A versus U-A structure, dynamics and open base pair kinetics.
  Nucleic Acids Res, 39, 767-780.  
21036872 M.I.Ponferrada-Marín, J.T.Parrilla-Doblas, T.Roldán-Arjona, and R.R.Ariza (2011).
A discontinuous DNA glycosylase domain in a family of enzymes that excise 5-methylcytosine.
  Nucleic Acids Res, 39, 1473-1484.  
19909758 D.O.Zharkov, G.V.Mechetin, and G.A.Nevinsky (2010).
Uracil-DNA glycosylase: Structural, thermodynamic and kinetic aspects of lesion search and recognition.
  Mutat Res, 685, 11-20.  
20927102 E.H.Rubinson, A.S.Gowda, T.E.Spratt, B.Gold, and B.F.Eichman (2010).
An unprecedented nucleic acid capture mechanism for excision of DNA damage.
  Nature, 468, 406-411.
PDB codes: 3jx7 3jxy 3jxz 3jy1
20083120 F.Faucher, S.S.Wallace, and S.Doublié (2010).
The C-terminal lysine of Ogg2 DNA glycosylases is a major molecular determinant for guanine/8-oxoguanine distinction.
  J Mol Biol, 397, 46-56.
PDB code: 3knt
20967294 M.Saharay, H.Guo, and J.C.Smith (2010).
Catalytic mechanism of cellulose degradation by a cellobiohydrolase, CelS.
  PLoS One, 5, e12947.  
20540060 M.Winnacker, V.Welzmiller, R.Strasser, and T.Carell (2010).
Development of a DNA photoaffinity probe for the analysis of 8-OxodG-binding proteins in a human proteome.
  Chembiochem, 11, 1345-1349.  
20071746 R.Amouroux, A.Campalans, B.Epe, and J.P.Radicella (2010).
Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions.
  Nucleic Acids Res, 38, 2878-2890.  
19889642 Y.Qi, M.C.Spong, K.Nam, M.Karplus, and G.L.Verdine (2010).
Entrapment and structure of an extrahelical guanine attempting to enter the active site of a bacterial DNA glycosylase, MutM.
  J Biol Chem, 285, 1468-1478.
PDB codes: 3jr4 3jr5
19444816 B.R.Brooks, C.L.Brooks, A.D.Mackerell, L.Nilsson, R.J.Petrella, B.Roux, Y.Won, G.Archontis, C.Bartels, S.Boresch, A.Caflisch, L.Caves, Q.Cui, A.R.Dinner, M.Feig, S.Fischer, J.Gao, M.Hodoscek, W.Im, K.Kuczera, T.Lazaridis, J.Ma, V.Ovchinnikov, E.Paci, R.W.Pastor, C.B.Post, J.Z.Pu, M.Schaefer, B.Tidor, R.M.Venable, H.L.Woodcock, X.Wu, W.Yang, D.M.York, and M.Karplus (2009).
CHARMM: the biomolecular simulation program.
  J Comput Chem, 30, 1545-1614.  
19145606 C.G.Yang, K.Garcia, and C.He (2009).
Damage detection and base flipping in direct DNA alkylation repair.
  Chembiochem, 10, 417-423.  
19446526 F.Faucher, S.Duclos, V.Bandaru, S.S.Wallace, and S.Doublié (2009).
Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinction.
  Structure, 17, 703-712.
PDB codes: 3fhf 3fhg
19361427 F.Faucher, S.M.Robey-Bond, S.S.Wallace, and S.Doublié (2009).
Structural characterization of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase in its apo form and in complex with 8-oxodeoxyguanosine.
  J Mol Biol, 387, 669-679.
PDB codes: 3f0z 3f10
18978813 K.A.Malecka, W.C.Ho, and R.Marmorstein (2009).
Crystal structure of a p53 core tetramer bound to DNA.
  Oncogene, 28, 325-333.
PDB codes: 3exj 3exl
19898474 P.C.Blainey, G.Luo, S.C.Kou, W.F.Mangel, G.L.Verdine, B.Bagchi, and X.S.Xie (2009).
Nonspecifically bound proteins spin while diffusing along DNA.
  Nat Struct Mol Biol, 16, 1224-1229.  
19740769 R.K.Neely, G.Tamulaitis, K.Chen, M.Kubala, V.Siksnys, and A.C.Jones (2009).
Time-resolved fluorescence studies of nucleotide flipping by restriction enzymes.
  Nucleic Acids Res, 37, 6859-6870.  
19841264 S.Lee, and G.L.Verdine (2009).
Atomic substitution reveals the structural basis for substrate adenine recognition and removal by adenine DNA glycosylase.
  Proc Natl Acad Sci U S A, 106, 18497-18502.
PDB code: 3g0q
19200715 S.Schneider, S.Schorr, and T.Carell (2009).
Crystal structure analysis of DNA lesion repair and tolerance mechanisms.
  Curr Opin Struct Biol, 19, 87-95.  
19674107 V.S.Sidorenko, A.P.Grollman, P.Jaruga, M.Dizdaroglu, and D.O.Zharkov (2009).
Substrate specificity and excision kinetics of natural polymorphic variants and phosphomimetic mutants of human 8-oxoguanine-DNA glycosylase.
  FEBS J, 276, 5149-5162.  
18281210 A.D.Mackerell, and L.Nilsson (2008).
Molecular dynamics simulations of nucleic acid-protein complexes.
  Curr Opin Struct Biol, 18, 194-199.  
18682218 B.R.Bowman, S.Lee, S.Wang, and G.L.Verdine (2008).
Structure of the E. coli DNA glycosylase AlkA bound to the ends of duplex DNA: a system for the structure determination of lesion-containing DNA.
  Structure, 16, 1166-1174.
PDB codes: 3cvs 3cvt 3cw7 3cwa 3cws 3cwt 3cwu
17992532 D.Vlcek, A.Sevcovicová, B.Sviezená, E.Gálová, and E.Miadoková (2008).
Chlamydomonas reinhardtii: a convenient model system for the study of DNA repair in photoautotrophic eukaryotes.
  Curr Genet, 53, 1.  
18408731 E.D.Garcin, D.J.Hosfield, S.A.Desai, B.J.Haas, M.Björas, R.P.Cunningham, and J.A.Tainer (2008).
DNA apurinic-apyrimidinic site binding and excision by endonuclease IV.
  Nat Struct Mol Biol, 15, 515-522.
PDB codes: 2nq9 2nqh 2nqj
18682223 G.Komazin-Meredith, R.J.Petrella, W.L.Santos, D.J.Filman, J.M.Hogle, G.L.Verdine, M.Karplus, and D.M.Coen (2008).
The human cytomegalovirus UL44 C clamp wraps around DNA.
  Structure, 16, 1214-1225.  
18820295 G.Tamulaitis, M.Zaremba, R.H.Szczepanowski, M.Bochtler, and V.Siksnys (2008).
How PspGI, catalytic domain of EcoRII and Ecl18kI acquire specificities for different DNA targets.
  Nucleic Acids Res, 36, 6101-6108.  
18072751 J.C.Delaney, and J.M.Essigmann (2008).
Biological properties of single chemical-DNA adducts: a twenty year perspective.
  Chem Res Toxicol, 21, 232-252.  
18353991 J.Hu, A.Ma, and A.R.Dinner (2008).
A two-step nucleotide-flipping mechanism enables kinetic discrimination of DNA lesions by AGT.
  Proc Natl Acad Sci U S A, 105, 4615-4620.  
18025045 J.M.Mundt, S.S.Hah, R.A.Sumbad, V.Schramm, and P.T.Henderson (2008).
Incorporation of extracellular 8-oxodG into DNA and RNA requires purine nucleoside phosphorylase in MCF-7 cells.
  Nucleic Acids Res, 36, 228-236.  
18000994 J.T.Stivers (2008).
Extrahelical damaged base recognition by DNA glycosylase enzymes.
  Chemistry, 14, 786-793.  
18219418 L.L.O'Neil, and O.Wiest (2008).
Sequence dependence in base flipping: experimental and computational studies.
  Org Biomol Chem, 6, 485-492.  
18154319 N.Krishnamurthy, K.Haraguchi, M.M.Greenberg, and S.S.David (2008).
Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases.
  Biochemistry, 47, 1043-1050.  
18686953 S.Lee, B.R.Bowman, Y.Ueno, S.Wang, and G.L.Verdine (2008).
Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine.
  J Am Chem Soc, 130, 11570-11571.
PDB code: 3d4v
18507380 S.Lee, C.T.Radom, and G.L.Verdine (2008).
Trapping and structural elucidation of a very advanced intermediate in the lesion-extrusion pathway of hOGG1.
  J Am Chem Soc, 130, 7784-7785.  
18557781 V.S.Sidorenko, G.V.Mechetin, G.A.Nevinsky, and D.O.Zharkov (2008).
Ionic strength and magnesium affect the specificity of Escherichia coli and human 8-oxoguanine-DNA glycosylases.
  FEBS J, 275, 3747-3760.  
18157156 W.Yang (2008).
Structure and mechanism for DNA lesion recognition.
  Cell Res, 18, 184-197.  
18588340 X.Zheng, J.Garcia, and A.A.Stuchebrukhov (2008).
Theoretical study of excitation energy transfer in DNA photolyase.
  J Phys Chem B, 112, 8724-8729.  
17114185 C.T.Radom, A.Banerjee, and G.L.Verdine (2007).
Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations.
  J Biol Chem, 282, 9182-9194.
PDB codes: 2nob 2noe 2nof 2noh 2noi 2nol 2noz
17307018 H.M.Senn, and W.Thiel (2007).
QM/MM studies of enzymes.
  Curr Opin Chem Biol, 11, 182-187.  
17704764 J.B.Parker, M.A.Bianchet, D.J.Krosky, J.I.Friedman, L.M.Amzel, and J.T.Stivers (2007).
Enzymatic capture of an extrahelical thymine in the search for uracil in DNA.
  Nature, 449, 433-437.
PDB codes: 2oxm 2oyt
17412704 J.Bischerour, and R.Chalmers (2007).
Base-flipping dynamics in a DNA hairpin processing reaction.
  Nucleic Acids Res, 35, 2584-2595.  
17531815 J.J.Warren, T.J.Pohlhaus, A.Changela, R.R.Iyer, P.L.Modrich, and L.S.Beese (2007).
Structure of the human MutSalpha DNA lesion recognition complex.
  Mol Cell, 26, 579-592.
PDB codes: 2o8b 2o8c 2o8d 2o8e 2o8f
17432829 L.Jia, V.Shafirovich, N.E.Geacintov, and S.Broyde (2007).
Lesion specificity in the base excision repair enzyme hNeil1: modeling and dynamics studies.
  Biochemistry, 46, 5305-5314.  
17529991 M.Yang, J.C.Culhane, L.M.Szewczuk, C.B.Gocke, C.A.Brautigam, D.R.Tomchick, M.Machius, P.A.Cole, and H.Yu (2007).
Structural basis of histone demethylation by LSD1 revealed by suicide inactivation.
  Nat Struct Mol Biol, 14, 535-539.
PDB code: 2uxn
17090545 N.A.Kuznetsov, V.V.Koval, G.A.Nevinsky, K.T.Douglas, D.O.Zharkov, and O.S.Fedorova (2007).
Kinetic conformational analysis of human 8-oxoguanine-DNA glycosylase.
  J Biol Chem, 282, 1029-1038.  
17284454 S.R.Bellamy, K.Krusong, and G.S.Baldwin (2007).
A rapid reaction analysis of uracil DNA glycosylase indicates an active mechanism of base flipping.
  Nucleic Acids Res, 35, 1478-1487.  
17581577 S.S.David, V.L.O'Shea, and S.Kundu (2007).
Base-excision repair of oxidative DNA damage.
  Nature, 447, 941-950.  
17194756 V.C.Pierre, J.T.Kaiser, and J.K.Barton (2007).
Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator.
  Proc Natl Acad Sci U S A, 104, 429-434.
PDB code: 2o1i
17417784 X.Jiao, J.Huang, S.Wu, M.Lv, Y.Hu, Jianfu, X.Su, C.Luo, and B.Ce (2007).
hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population.
  Int J Cancer, 121, 501-505.  
17015827 A.Banerjee, and G.L.Verdine (2006).
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex.
  Proc Natl Acad Sci U S A, 103, 15020-15025.
PDB code: 2i5w
16497933 A.Banerjee, W.L.Santos, and G.L.Verdine (2006).
Structure of a DNA glycosylase searching for lesions.
  Science, 311, 1153-1157.
PDB codes: 2f5n 2f5o 2f5p 2f5q 2f5s
16500982 A.Krueger, E.Protozanova, and M.D.Frank-Kamenetskii (2006).
Sequence-dependent base pair opening in DNA double helix.
  Biophys J, 90, 3091-3099.  
17017766 C.Cao, Y.L.Jiang, D.J.Krosky, and J.T.Stivers (2006).
The catalytic power of uracil DNA glycosylase in the opening of thymine base pairs.
  J Am Chem Soc, 128, 13034-13035.  
16888824 H.A.Wagenknecht (2006).
The search for single DNA damage among millions of base pairs: DNA glycosylases trapped at work.
  Angew Chem Int Ed Engl, 45, 5583-5585.  
16452614 H.Takinowaki, Y.Matsuda, T.Yoshida, Y.Kobayashi, and T.Ohkubo (2006).
The solution structure of the methylated form of the N-terminal 16-kDa domain of Escherichia coli Ada protein.
  Protein Sci, 15, 487-497.
PDB code: 1wpk
16524590 J.R.Horton, K.Liebert, M.Bekes, A.Jeltsch, and X.Cheng (2006).
Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase.
  J Mol Biol, 358, 559-570.
PDB code: 2g1p
17312959 M.L.Hamm, and K.Billig (2006).
Synthesis, oligonucleotide incorporation and base pair stability of 7-methyl-8-oxo-2'-deoxyguanosine.
  Org Biomol Chem, 4, 4068-4070.  
16984202 M.T.Bennett, M.T.Rodgers, A.S.Hebert, L.E.Ruslander, L.Eisele, and A.C.Drohat (2006).
Specificity of human thymine DNA glycosylase depends on N-glycosidic bond stability.
  J Am Chem Soc, 128, 12510-12519.  
16698780 M.Zacharias (2006).
Minor groove deformability of DNA: a molecular dynamics free energy simulation study.
  Biophys J, 91, 882-891.  
16585517 P.C.Blainey, A.M.van Oijen, A.Banerjee, G.L.Verdine, and X.S.Xie (2006).
A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA.
  Proc Natl Acad Sci U S A, 103, 5752-5757.  
17115714 R.K.Walker, A.K.McCullough, and R.S.Lloyd (2006).
Uncoupling of nucleotide flipping and DNA bending by the t4 pyrimidine dimer DNA glycosylase.
  Biochemistry, 45, 14192-14200.  
17022941 R.Radhakrishnan, and T.Schlick (2006).
Correct and incorrect nucleotide incorporation pathways in DNA polymerase beta.
  Biochem Biophys Res Commun, 350, 521-529.  
16495121 V.L.Yip, and S.G.Withers (2006).
Breakdown of oligosaccharides by the process of elimination.
  Curr Opin Chem Biol, 10, 147-155.  
17053070 X.Zhang, and T.C.Bruice (2006).
Reaction mechanism of guanidinoacetate methyltransferase, concerted or step-wise.
  Proc Natl Acad Sci U S A, 103, 16141-16146.  
16464003 Y.Mishina, E.M.Duguid, and C.He (2006).
Direct reversal of DNA alkylation damage.
  Chem Rev, 106, 215-232.  
16085769 C.Yuan, E.Rhoades, D.M.Heuer, and L.A.Archer (2005).
Mismatch-induced DNA unbending upon duplex opening.
  Biophys J, 89, 2564-2573.  
16061814 J.Shen, D.Gai, A.Patrick, W.B.Greenleaf, and X.S.Chen (2005).
The roles of the residues on the channel beta-hairpin and loop structures of simian virus 40 hexameric helicase.
  Proc Natl Acad Sci U S A, 102, 11248-11253.  
15809645 M.Montoya (2005).
The interrogator.
  Nat Struct Mol Biol, 12, 284.  
16174844 P.Macpherson, F.Barone, G.Maga, F.Mazzei, P.Karran, and M.Bignami (2005).
8-oxoguanine incorporation into DNA repeats in vitro and mismatch recognition by MutSalpha.
  Nucleic Acids Res, 33, 5094-5105.  
16340006 R.K.Neely, D.Daujotyte, S.Grazulis, S.W.Magennis, D.T.Dryden, S.Klimasauskas, and A.C.Jones (2005).
Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M.HhaI-DNA complexes.
  Nucleic Acids Res, 33, 6953-6960.
PDB codes: 2c7o 2c7p 2c7q 2c7r
15800603 S.S.David (2005).
Structural biology: DNA search and rescue.
  Nature, 434, 569-570.  
16332091 Y.L.Jiang, D.J.Krosky, L.Seiple, and J.T.Stivers (2005).
Uracil-directed ligand tethering: an efficient strategy for uracil DNA glycosylase (UNG) inhibitor development.
  J Am Chem Soc, 127, 17412-17420.  
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 codes are shown on the right.