Abstract:
:Molecular interactions between the tumor suppressor p53 and the transcriptional coactivators CBP/p300 are critical for the regulation of p53 transactivation and stability. The transactivation domain (TAD) of p53 binds directly to several CBP/p300 domains (TAZ1, TAZ2, NCBD, and KIX). Here we map the interaction between the p53 TAD and the CBP KIX domain using isothermal titration calorimetry and NMR spectroscopy. KIX is a structural domain in CBP/p300 that can simultaneously bind two polypeptide ligands, such as the activation domain of MLL and the kinase-inducible activation domain (pKID) of CREB, using distinct interaction surfaces. The p53 TAD consists of two subdomains (AD1 and AD2); peptides corresponding to the isolated AD1 and AD2 subdomains interact with KIX with relatively low affinity, but a longer peptide containing both subdomains binds KIX tightly. In the context of the full-length p53 TAD, AD1 and AD2 bind synergistically to KIX. Mapping of the chemical shift perturbations onto the structure of KIX shows that isolated AD1 and AD2 peptides bind to both the MLL and pKID sites. Spin-labeling experiments show that the complex of the full-length p53 TAD with KIX is disordered, with the AD1 and AD2 subdomains each interacting with both the MLL and pKID binding surfaces. Phosphorylation of the p53 TAD at Thr18 or Ser20 increases the KIX binding affinity. The affinity is further enhanced by simultaneous phosphorylation of Thr18 and Ser20, and the specificity of the interaction is increased. The p53 TAD simultaneously occupies the two distinct sites that have been identified on the CBP KIX domain and efficiently competes for these sites with other known KIX-binding transcription factors.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Lee CW,Arai M,Martinez-Yamout MA,Dyson HJ,Wright PEdoi
10.1021/bi802055vsubject
Has Abstractpub_date
2009-03-17 00:00:00pages
2115-24issue
10eissn
0006-2960issn
1520-4995pii
10.1021/bi802055vjournal_volume
48pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Ribonuclease P2 from the thermophilic archaebacterium Sulfolobus solfataricus is a small protein (7 kDa) with a known three-dimensional structure. Inspection of the structure and molecular dynamics simulation reveal that three aromatic residues (Phe5, Phe31, and Tyr33) from the hydrophobic core have a strong van der W...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970467v
更新日期:1997-07-22 00:00:00
abstract::Troponin T (TnT) is an essential element in the thin filament-based regulatory system of striated muscle. Alternative mRNA splicing generates multiple TnT isoforms with primary structural differences in the NH2-terminal region. The functional significance of this hypervariable NH2-terminal domain and the developmental...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9812322
更新日期:1998-10-13 00:00:00
abstract::Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0200514
更新日期:2002-05-21 00:00:00
abstract::Thermococcus litoralis 4-alpha-glucanotransferase (TLGT) belongs to family 57 of glycoside hydrolases and catalyzes the disproportionation and cycloamylose synthesis reactions. Family 57 glycoside hydrolases have not been well investigated, and even the catalytic mechanism involving the active site residues has not be...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011017c
更新日期:2001-10-16 00:00:00
abstract::CNAD (5-beta-D-ribofuranosylnicotinamide adenine dinucleotide) is an isosteric C-glycosidic analogue of NAD(H) containing a neutral pyridine ring. CPAD (5-beta-D-ribofuranosylpicolinamide adenine dinucleotide) is a closely related pyridine-containing analogue with the pyridine nitrogen on the opposite side of the ring...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00205a009
更新日期:1994-10-04 00:00:00
abstract::Tissue plasminogen activator-inhibitor complexes were purified from the conditioned medium of human umbilical vein endothelial cells by affinity chromatography followed by gel filtration. It was found that a single complex was isolated which can exist in two distinct interconvertible conformations. These may be separa...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00397a037
更新日期:1987-11-17 00:00:00
abstract::The interaction of glutamyl-tRNA synthetase with tRNAGlu2 has been studied. The enzyme was purified to apparent homogeneity, and consists of a single chain with a molecular weight of 59 000. The sedimentation coefficient (sdegrees20,w) was found to be 3.7 S and suggests this enzyme is quite asymmetric. The enzyme bind...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00664a032
更新日期:1976-09-21 00:00:00
abstract::The prion protein (PrP) is a cell-surface Cu2+ binding glycoprotein which can bind six copper ions. The role of Cu2+ in PrP function, misfolding, and prion disease has generated much interest; however, the field has been hampered by a lack of consensus with regard to the affinity of Cu2+ for PrPC. Here we build on our...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9011397
更新日期:2009-09-29 00:00:00
abstract::The actin depolymerizing factor (ADF)/cofilins are an essential group of proteins that are important regulators of actin filament turnover in vivo. Although protists and yeasts express only a single member of this family, metazoans express two or more members in many cell types. In cells expressing both ADF and cofili...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049797n
更新日期:2004-06-08 00:00:00
abstract::Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100922r
更新日期:2010-08-17 00:00:00
abstract::The pigment composition of the isolated photosystem II reaction center complex in its most stable and pure form currently is a matter of considerable debate. In this contribution, we present a new method based on a combination of gel filtration chromatography and diode array detection to analyze the composition of pho...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960991m
更新日期:1996-10-01 00:00:00
abstract::The contributions to thermostability of interactions within the beta-sheet region of rubredoxins (Rds) were investigated by examining proteins in which beta-strand sequences of Rds from the hyperthermophilic archaeon Pyrococcus furiosus (Pf) and the mesophilic bacterium Clostridium pasteurianum (Cp) were interchanged....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970110r
更新日期:1997-08-26 00:00:00
abstract::Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00215a025
更新日期:1991-01-08 00:00:00
abstract::Dihydroorotate dehydrogenases (DHODs) oxidize dihydroorotate (DHO) to orotate using the FMN prosthetic group to abstract a hydride equivalent from C6 and a protein residue (Ser for Class 2 DHODs) to deprotonate C5. The fundamental question of whether the scission of the two DHO C-H bonds is concerted or stepwise was a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060919g
更新日期:2006-12-19 00:00:00
abstract::Thermobifida fusca Cel9A-90, an unusual family 9 enzyme, is a processive endoglucanase containing a catalytic domain closely linked to a family 3c cellulose binding domain (Cel9A-68) followed by a fibronectin III-like domain and a family 2 cellulose binding domain. To study its catalytic mechanism, 12 mutant genes wit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049394n
更新日期:2004-08-03 00:00:00
abstract::The major covalently linked multimolecular D fragments found in plasmic digests of factor XIIIa cross-linked fibrin formed under physiological pH and ionic strength conditions consist of D dimers, D trimers, and D tetramers. These fragments are linked by epsilon-amino-gamma-glutamyllysine bonds in the carboxy-terminal...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00118a040
更新日期:1992-01-28 00:00:00
abstract::The beta 2-adrenergic receptor (beta 2AR) is a member of a large superfamily of seven transmembrane domain, G-protein-coupled receptors. Within the putative seventh transmembrane domain of the beta 2AR is a sequence of amino acids, NPLIY, which is conserved with minor variations in all members of the superfamily. Prev...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00047a003
更新日期:1995-11-28 00:00:00
abstract::We obtained a novel carbohydrate-binding peptide having a helix-loop-helix scaffold from a random peptide library. The helix-loop-helix peptide library randomized at five amino acid residues was displayed on the major coat protein of a filamentous phage. Affinity selection with a ganglioside, Galbeta1-3GalNAcbeta1-4(N...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8000837
更新日期:2008-07-01 00:00:00
abstract::We have combined three mutations previously shown to stabilize lambda repressor against thermal denaturation. Two of these mutations are in helix 3, where Gly-46 and Gly-48 have been replaced by alanines [Hecht, M. H., et al. (1986) Proteins: Struct., Funct., Genet. 1, 43-46]. The other mutation, which replaces Tyr-88...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00419a059
更新日期:1988-09-20 00:00:00
abstract::The structures of the modified folates present in Pyrococcus furiosus have been determined. This was accomplished largely by the characterization of the arylamines resulting from the air oxidative cleavage of the reduced modified folates present in these cells, using both chemical and enzymatic methods. Cell extracts ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00054a003
更新日期:1993-01-26 00:00:00
abstract::Human apolipoprotein(a) kringle IV type 10 [apo(a) KIV(10)] contains a strong lysine-binding site (LBS) that mediates the interaction of Lp(a) with biological substrates such as fibrin. Mutations in the KIV(10) LBS have been reported in both the rhesus monkey and chimpanzee, and have been proposed to explain the lack ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048156p
更新日期:2005-01-18 00:00:00
abstract::We systematically and quantitatively investigated the structure and thermodynamics of G-quadruplexes of RNAs and corresponding DNAs of the same sequences under molecular crowding conditions that mimic the high osmotic stress induced by the numerous molecules inside of living cells. Structural analyses demonstrated tha...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1002822
更新日期:2010-06-01 00:00:00
abstract::Minor adducts, derived from the covalent binding of anti-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide to cellular DNA, may play an important role in generating mutations and initiating cancer. We have applied a combined NMR-computational approach including intensity based refinement to determine the solution structure of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991212f
更新日期:1999-08-17 00:00:00
abstract::Affinity selection-mass spectrometry (AS-MS) screening of kinesin spindle protein (KSP) followed by enzyme inhibition studies and temperature-dependent circular dichroism (TdCD) characterization was utilized to identify a series of benzimidazole compounds. This series also binds in the presence of Ispinesib, a known a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1005283
更新日期:2010-09-28 00:00:00
abstract::The kinetic and thermodynamic features of reactions catalyzed by present-day enzymes appear to be the consequence of the evolution of these proteins toward maximal catalytic effectiveness. These features are identified and analyzed (in detail for one substrate-one product enzymes) by using ideas that link the energeti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00450a009
更新日期:1989-11-28 00:00:00
abstract::It has been shown (Poole et al., 1991) that deletion of residues 44-49 from the sequence of staphylococcal nuclease (E43 SNase) results in an enzyme (E43 delta SNase) that is significantly more active than D43 SNase, an enzyme that differs from the wild-type enzyme by deletion of a single methylene group. In addition,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00229a006
更新日期:1991-04-16 00:00:00
abstract::Spectrin dimers interact weakly with F-actin under physiological solvent conditions (with an association constant of about 5 X 10(3) M-1 at 20 degrees C). In the presence of the membrane skeletal constituent, protein 4.1, strong binding is observed; an analysis of the profiles for formation of a ternary complex leads ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00314a027
更新日期:1984-09-11 00:00:00
abstract::The structural features of a chemically modified DNA template strand may promote error-prone DNA synthesis during replication. The resulting higher incidence of mutations, in turn, can eventually lead to tumor initiation. Structural insights into this process can be monitored by studying chemically modified base adduc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00046a043
更新日期:1995-11-21 00:00:00
abstract::The product of yjeK in Escherichia coli is a homologue of lysine 2,3-aminomutase (LAM) from Clostridium subterminale SB4, and both enzymes catalyze the isomerization of (S)- but not (R)-alpha-lysine by radical mechanisms. The turnover number for LAM from E. coli is 5.0 min(-1), 0.1% of the value for clostridial LAM. T...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061328t
更新日期:2006-10-24 00:00:00
abstract::There has been intense interest in the development of factor Xa inhibitors for the treatment of thrombotic diseases. Our laboratory has developed a series of novel non-amidine inhibitors of factor Xa. This paper presents two crystal structures of compounds from this series bound to factor Xa. The first structure is de...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0264061
更新日期:2002-12-31 00:00:00