PDBsum entry 5rhn

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Nucleotide-binding protein PDB id
Protein chain
115 a.a. *
Waters ×51
* Residue conservation analysis
PDB id:
Name: Nucleotide-binding protein
Title: Histidine triad nucleotide-binding protein (hint) from rabbi complexed with 8-br-amp
Structure: Histidine triad nucleotide-binding protein. Chain: a. Synonym: hint. Engineered: yes
Source: Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Organ: heart. Gene: hint. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: rabbit hint cdna was cloned from heart libra expressed in escherichia coli, and purified by adenosine-ag
Biol. unit: Dimer (from PDB file)
2.31Å     R-factor:   0.162     R-free:   0.264
Authors: C.Brenner,P.Garrison,J.Gilmour,D.Peisach,D.Ringe,G.A.Petsko, J.M.Lowenstein
Key ref: C.Brenner et al. (1997). Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nat Struct Biol, 4, 231-238. PubMed id: 9164465
26-Feb-97     Release date:   16-Jun-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P80912  (HINT1_RABIT) -  Histidine triad nucleotide-binding protein 1
126 a.a.
115 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     signal transduction by p53 class mediator resulting in induction of apoptosis   5 terms 
  Biochemical function     catalytic activity     3 terms  


Nat Struct Biol 4:231-238 (1997)
PubMed id: 9164465  
Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
C.Brenner, P.Garrison, J.Gilmour, D.Peisach, D.Ringe, G.A.Petsko, J.M.Lowenstein.
Histidine triad nucleotide-binding protein (HINT), a dimeric purine nucleotide-binding protein from rabbit heart, is a member of the HIT (histidine triad) superfamily which includes HINT homologues and FHIT (HIT protein encoded at the chromosome 3 fragile site) homologues. Crystal structures of HINT-nucleotide complexes demonstrate that the most conserved residues in the superfamily mediate nucleotide binding and that the HIT motif forms part of the phosphate binding loop. Galactose-1-phosphate uridylyltransferase, whose deficiency causes galactosemia, contains tandem HINT domains with the same fold and mode of nucleotide binding as HINT despite having no overall sequence similarity. Features of FHIT, a diadenosine polyphosphate hydrolase and candidate tumour suppressor, are predicted from HINT-nucleotide structures.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21316334 J.Martin, M.V.St-Pierre, and J.F.Dufour (2011).
Hit proteins, mitochondria and cancer.
  Biochim Biophys Acta, 1807, 626-632.  
20033706 M.I.Hassan, A.Naiyer, and F.Ahmad (2010).
Fragile histidine triad protein: structure, function, and its association with tumorogenesis.
  J Cancer Res Clin Oncol, 136, 333-350.  
19541768 H.Banerjee, J.B.Palenchar, M.Lukaszewicz, E.Bojarska, J.Stepinski, J.Jemielity, A.Guranowski, S.Ng, D.A.Wah, E.Darzynkiewicz, and V.Bellofatto (2009).
Identification of the HIT-45 protein from Trypanosoma brucei as an FHIT protein/dinucleoside triphosphatase: substrate specificity studies on the recombinant and endogenous proteins.
  RNA, 15, 1554-1564.  
18836178 U.Rass, I.Ahel, and S.C.West (2008).
Molecular mechanism of DNA deadenylation by the neurological disease protein aprataxin.
  J Biol Chem, 283, 33994-34001.  
17498066 I.Carmi, and E.Razin (2007).
The role played by key transcription factors in activated mast cells.
  Immunol Rev, 217, 280-291.  
17158446 T.F.Chou, and C.R.Wagner (2007).
Lysyl-tRNA synthetase-generated lysyl-adenylate is a substrate for histidine triad nucleotide binding proteins.
  J Biol Chem, 282, 4719-4727.  
17337452 T.F.Chou, I.B.Tikh, B.A.Horta, B.Ghosh, R.B.De Alencastro, and C.R.Wagner (2007).
Engineered monomeric human histidine triad nucleotide-binding protein 1 hydrolyzes fluorogenic acyl-adenylate and lysyl-tRNA synthetase-generated lysyl-adenylate.
  J Biol Chem, 282, 15137-15147.  
17485667 W.A.Laing, M.A.Wright, J.Cooney, and S.M.Bulley (2007).
The missing step of the L-galactose pathway of ascorbate biosynthesis in plants, an L-galactose guanyltransferase, increases leaf ascorbate content.
  Proc Natl Acad Sci U S A, 104, 9534-9539.  
17419878 Y.Wei, J.Ko, L.F.Murga, and M.J.Ondrechen (2007).
Selective prediction of interaction sites in protein structures with THEMATICS.
  BMC Bioinformatics, 8, 119.  
16186798 H.Li, Y.Zhang, T.Su, R.M.Santella, and I.B.Weinstein (2006).
Hint1 is a haplo-insufficient tumor suppressor in mice.
  Oncogene, 25, 713-721.  
16519510 J.G.McCoy, A.Arabshahi, E.Bitto, C.A.Bingman, F.J.Ruzicka, P.A.Frey, and G.N.Phillips (2006).
Structure and mechanism of an ADP-glucose phosphorylase from Arabidopsis thaliana.
  Biochemistry, 45, 3154-3162.
PDB codes: 1z84 1zwj
16762638 J.Martin, F.Magnino, K.Schmidt, A.C.Piguet, J.S.Lee, D.Semela, M.V.St-Pierre, A.Ziemiecki, D.Cassio, C.Brenner, S.S.Thorgeirsson, and J.F.Dufour (2006).
Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma.
  Gastroenterology, 130, 2179-2188.  
16835243 J.Weiske, and O.Huber (2006).
The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity.
  J Biol Chem, 281, 27356-27366.  
  17142912 W.T.Lo, K.H.Chin, H.L.Shr, F.P.Gao, P.C.Lyu, A.H.Wang, and S.H.Chou (2006).
Crystallization and preliminary X-ray analysis of XC1015, a histidine triad-like protein from Xanthomonas campestris.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1263-1265.  
15904496 M.Hopfe, J.H.Hegemann, and B.Henrich (2005).
HinT proteins and their putative interaction partners in Mollicutes and Chlamydiaceae.
  BMC Microbiol, 5, 27.  
15703176 T.F.Chou, P.Bieganowski, K.Shilinski, J.Cheng, C.Brenner, and C.R.Wagner (2005).
31P NMR and genetic analysis establish hinT as the only Escherchia coli purine nucleoside phosphoramidase and as essential for growth under high salt conditions.
  J Biol Chem, 280, 15356-15361.  
16199869 Y.N.Lee, and E.Razin (2005).
Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells.
  Mol Cell Biol, 25, 8904-8912.  
14982931 A.Krakowiak, H.C.Pace, G.M.Blackburn, M.Adams, A.Mekhalfia, R.Kaczmarek, J.Baraniak, W.J.Stec, and C.Brenner (2004).
Biochemical, crystallographic, and mutagenic characterization of hint, the AMP-lysine hydrolase, with novel substrates and inhibitors.
  J Biol Chem, 279, 18711-18716.
PDB code: 1rzy
15507519 K.P.Parks, H.Seidle, N.Wright, J.B.Sperry, P.Bieganowski, K.Howitz, D.L.Wright, and C.Brenner (2004).
Altered specificity of Hint-W123Q supports a role for Hint inhibition by ASW in avian sex determination.
  Physiol Genomics, 20, 12-14.  
15273322 S.W.Liu, X.Jiao, H.Liu, M.Gu, C.D.Lima, and M.Kiledjian (2004).
Functional analysis of mRNA scavenger decapping enzymes.
  RNA, 10, 1412-1422.  
12871939 D.A.Kwasnicka, A.Krakowiak, C.Thacker, C.Brenner, and S.R.Vincent (2003).
Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1.
  J Biol Chem, 278, 39051-39058.  
12574506 F.Trapasso, A.Krakowiak, R.Cesari, J.Arkles, S.Yendamuri, H.Ishii, A.Vecchione, T.Kuroki, P.Bieganowski, H.C.Pace, K.Huebner, C.M.Croce, and C.Brenner (2003).
Designed FHIT alleles establish that Fhit-induced apoptosis in cancer cells is limited by substrate binding.
  Proc Natl Acad Sci U S A, 100, 1592-1597.  
12620103 H.C.Pace, and C.Brenner (2003).
Feminizing chicks: a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer.
  Genome Biol, 4, R18.  
12810953 T.Su, M.Suzui, L.Wang, C.S.Lin, W.Q.Xing, and I.B.Weinstein (2003).
Deletion of histidine triad nucleotide-binding protein 1/PKC-interacting protein in mice enhances cell growth and carcinogenesis.
  Proc Natl Acad Sci U S A, 100, 7824-7829.  
12119013 C.Brenner (2002).
Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases.
  Biochemistry, 41, 9003-9014.  
12198172 H.Liu, N.D.Rodgers, X.Jiao, and M.Kiledjian (2002).
The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases.
  EMBO J, 21, 4699-4708.  
  12028594 M.Rubio-Texeira, J.M.Varnum, P.Bieganowski, and C.Brenner (2002).
Control of dinucleoside polyphosphates by the FHIT-homologous HNT2 gene, adenine biosynthesis and heat shock in Saccharomyces cerevisiae.
  BMC Mol Biol, 3, 7.  
11805111 P.Bieganowski, P.N.Garrison, S.C.Hodawadekar, G.Faye, L.D.Barnes, and C.Brenner (2002).
Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3.
  J Biol Chem, 277, 10852-10860.  
11877379 R.Lemaire, J.Prasad, T.Kashima, J.Gustafson, J.L.Manley, and R.Lafyatis (2002).
Stability of a PKCI-1-related mRNA is controlled by the splicing factor ASF/SF2: a novel function for SR proteins.
  Genes Dev, 16, 594-607.  
11454219 A.Kitzerow, and B.Henrich (2001).
The cytosolic HinT protein of Mycoplasma hominis interacts with two membrane proteins.
  Mol Microbiol, 41, 279-287.  
10671479 A.Draganescu, S.C.Hodawadekar, K.R.Gee, and C.Brenner (2000).
Fhit-nucleotide specificity probed with novel fluorescent and fluorogenic substrates.
  J Biol Chem, 275, 4555-4560.  
11007992 A.G.McLennan (2000).
Dinucleoside polyphosphates-friend or foe?
  Pharmacol Ther, 87, 73-89.  
11007995 A.Guranowski (2000).
Specific and nonspecific enzymes involved in the catabolism of mononucleoside and dinucleoside polyphosphates.
  Pharmacol Ther, 87, 117-139.  
10959838 H.C.Pace, S.C.Hodawadekar, A.Draganescu, J.Huang, P.Bieganowski, Y.Pekarsky, C.M.Croce, and C.Brenner (2000).
Crystal structure of the worm NitFhit Rosetta Stone protein reveals a Nit tetramer binding two Fhit dimers.
  Curr Biol, 10, 907-917.
PDB code: 1ems
  11029061 T.Hori, S.Asakawa, Y.Itoh, N.Shimizu, and S.Mizuno (2000).
Wpkci, encoding an altered form of PKCI, is conserved widely on the avian W chromosome and expressed in early female embryos: implication of its role in female sex determination.
  Mol Biol Cell, 11, 3645-3660.  
10090754 A.Abend, P.N.Garrison, L.D.Barnes, and P.A.Frey (1999).
Stereochemical retention of the configuration in the action of Fhit on phosphorus-chiral substrates.
  Biochemistry, 38, 3668-3676.  
10497298 C.Brenner, P.Bieganowski, H.C.Pace, and K.Huebner (1999).
The histidine triad superfamily of nucleotide-binding proteins.
  J Cell Physiol, 181, 179-187.  
10215898 E.A.Atencia, O.Madrid, M.A.Günther Sillero, and A.Sillero (1999).
T4 RNA ligase catalyzes the synthesis of dinucleoside polyphosphates.
  Eur J Biochem, 261, 802-811.  
10085096 J.L.Cartwright, and A.G.McLennan (1999).
The Saccharomyces cerevisiae YOR163w gene encodes a diadenosine 5', 5"'-P1,P6-hexaphosphate (Ap6A) hydrolase member of the MutT motif (Nudix hydrolase) family.
  J Biol Chem, 274, 8604-8610.  
9576908 H.C.Pace, P.N.Garrison, A.K.Robinson, L.D.Barnes, A.Draganescu, A.Rösler, G.M.Blackburn, Z.Siprashvili, C.M.Croce, K.Huebner, and C.Brenner (1998).
Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit.
  Proc Natl Acad Sci U S A, 95, 5484-5489.
PDB codes: 1fhi 2fhi
9928473 K.Huebner, P.N.Garrison, L.D.Barnes, and C.M.Croce (1998).
The role of the FHIT/FRA3B locus in cancer.
  Annu Rev Genet, 32, 7.  
9671749 Y.Pekarsky, M.Campiglio, Z.Siprashvili, T.Druck, Y.Sedkov, S.Tillib, A.Draganescu, P.Wermuth, J.H.Rothman, K.Huebner, A.M.Buchberg, A.Mazo, C.Brenner, and C.M.Croce (1998).
Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans.
  Proc Natl Acad Sci U S A, 95, 8744-8749.  
9543008 C.Brenner, H.C.Pace, P.N.Garrison, A.K.Robinson, A.Rosler, X.H.Liu, G.M.Blackburn, C.M.Croce, K.Huebner, and L.D.Barnes (1997).
Purification and crystallization of complexes modeling the active state of the fragile histidine triad protein.
  Protein Eng, 10, 1461-1463.  
9261067 C.D.Lima, K.L.D'Amico, I.Naday, G.Rosenbaum, E.M.Westbrook, and W.A.Hendrickson (1997).
MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family.
  Structure, 5, 763-774.
PDB codes: 1fit 2fit 3fit
9391102 Z.Siprashvili, G.Sozzi, L.D.Barnes, P.McCue, A.K.Robinson, V.Eryomin, L.Sard, E.Tagliabue, A.Greco, L.Fusetti, G.Schwartz, M.A.Pierotti, C.M.Croce, and K.Huebner (1997).
Replacement of Fhit in cancer cells suppresses tumorigenicity.
  Proc Natl Acad Sci U S A, 94, 13771-13776.  
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