Abstract:
:A major biochemical goal is the ability to mimic nature in engineering highly specific protein-protein interactions (PPIs). We previously devised a computational interactome screen to identify eight peptides that form four heterospecific dimers despite 32 potential off-targets. To expand the speed and utility of our approach and the PPI toolkit, we have developed new software to derive much larger heterospecific sets (≥24 peptides) while directing against antiparallel off-targets. It works by predicting Tm values for every dimer on the basis of core, electrostatic, and helical propensity components. These guide interaction specificity, allowing heterospecific coiled coil (CC) sets to be incrementally assembled. Prediction accuracy is experimentally validated using circular dichroism and size exclusion chromatography. Thermal denaturation data from a 22-CC training set were used to improve software prediction accuracy and verified using a 136-CC test set consisting of eight predicted heterospecific dimers and 128 off-targets. The resulting software, qCIPA, individually now weighs core a-a' (II/NN/NI) and electrostatic g-e'+1 (EE/EK/KK) components. The expanded data set has resulted in emerging sequence context rules for otherwise energetically equivalent CCs; for example, introducing intrahelical electrostatic charge blocks generated increased stability for designed CCs while concomitantly decreasing the stability of off-target CCs. Coupled with increased prediction accuracy and speed, the approach can be applied to a wide range of downstream chemical and synthetic biology applications, in addition more generally to impose specificity on structurally unrelated PPIs.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Crooks RO,Lathbridge A,Panek AS,Mason JMdoi
10.1021/acs.biochem.7b00047subject
Has Abstractpub_date
2017-03-21 00:00:00pages
1573-1584issue
11eissn
0006-2960issn
1520-4995journal_volume
56pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Information on the secondary structure and interactions of RNA is important to understand the biological function of RNA as well as in applying RNA as a tool for therapeutic purposes. Recently, the isoenergetic microarray mapping method was developed to improve the prediction of RNA secondary structure. Herein, for th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200463p
更新日期:2011-09-06 00:00:00
abstract::Double homeodomain (DUX) proteins are encoded by a family of 3.3-kilobase repeated elements dispersed in the human genome. One of these elements named D4Z4 is found in a tandem repeat array on chromosome 4 that is partially deleted in facioscapulohumeral muscular dystrophy. We have evaluated the trafficking and mobili...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047992w
更新日期:2005-02-22 00:00:00
abstract::The solution nuclear magnetic resonance (NMR) structures and backbone (15)N dynamics of the specialized acyl carrier protein (ACP), RpAcpXL, from Rhodopseudomonas palustris, in both the apo form and holo form modified by covalent attachment of 4'-phosphopantetheine at S37, are virtually identical, monomeric, and corre...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300546b
更新日期:2012-09-18 00:00:00
abstract::Tetraheme cytochromes involved in photosynthetic electron transport have previously been described associated with the reaction centers of purple photosynthetic bacteria; however, similar heme proteins have not until now been characterized in the phylogenetically distinct green sulfur bacteria. In this paper we descri...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962624g
更新日期:1997-02-18 00:00:00
abstract::Second-harmonic light scattering (SHS) permits characterization of membrane-specific molecular transport in living cells. Herein, we demonstrate the use of time-resolved SHS for quantifying chemically induced enhancements in membrane permeability. As proof of concept, we examine the enhanced permeability of the cytopl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00600
更新日期:2015-07-28 00:00:00
abstract::The recognition sequence of the Myb protein has been recently described to be pyAACKGHH (where py = T/C, K = G/T, and H = A/C/T), modifying the earlier identification as pyAACKG [Ording, E., et al. (1994) Eur. J. Biochem. 222, 113-120]. We had earlier determined the solution structure of the minimal cognate sequence T...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9806753
更新日期:1998-07-14 00:00:00
abstract::Tombusviruses use a 19 kDa protein (p19) as a suppressor of the RNA silencing pathway during infection. The p19 protein binds to short-interfering RNA (siRNA) as a dimer and shows a high selectivity for short duplex RNAs over other RNA species. Since p19 can bind to synthetic and RNA silencing generated small RNAs wit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi800401y
更新日期:2008-08-05 00:00:00
abstract::The occurrence of isozymes in plant peroxidases is poorly understood. Turnip roots contain seven season-dependent isoperoxidases with distinct physicochemical properties. In the work presented here, multifrequency electron paramagnetic resonance spectroscopy has been used to characterize the Compound I intermediate ob...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002826j
更新日期:2001-06-12 00:00:00
abstract::The light-induced global conformational change of photoactive yellow protein was directly observed by small-angle X-ray scattering (SAXS). The N-terminal 6, 15, or 23 amino acid residues were enzymatically truncated (T6, T15, or T23, respectively), and their near-UV intermediates were accumulated under continuous illu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0264768
更新日期:2002-11-19 00:00:00
abstract::The voltage-sensitive sodium channel is an intrinsic membrane protein that is nonrandomly distributed in neurons, suggesting a possible interaction with other cellular constituents. In this study, we have directly tested the hypothesis that components of the cytoskeleton interact with sodium channels. Utilizing the me...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00406a003
更新日期:1988-03-22 00:00:00
abstract::Benzo[c]phenanthrene diol epoxide can covalently bind to the exocyclic amino group of deoxyadenosine to generate [BPh]dA adducts where the polycyclic aromatic hydrocarbon is attached to the major groove edge of DNA. This paper reports on NMR-energy minimization structural studies of the (+)-trans-anti-[BPh]dA adduct p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00097a029
更新日期:1993-11-23 00:00:00
abstract::The reversible inhibition of beta-lactamase I from Bacillus cereus by cloxacillin, methicillin, and nafcillin has been systematically investigated. For these substrates the enzymatic reaction involves partitioning of the substrate between turnover and inhibition. Typically, concentrations of several hundred millimolar...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00388a011
更新日期:1987-07-14 00:00:00
abstract::The natural product hypericin is a photosensitive polycyclic aromatic dione compound, which has been widely investigated because of its virucidal and antitumor properties. Although it has been suggested that singlet oxygen or a radical species might be responsible for its biological action, its mechanism of action rem...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991147+
更新日期:1999-08-31 00:00:00
abstract::Oligonucleotides capable of sequence-specific triple helix formation have been proposed as DNA binding ligands useful for modulation of gene expression and for directed genome modification. However, the effectiveness of such triplex-forming oligonucleotides (TFOs) depends on their ability to bind to their target sites...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982290q
更新日期:1999-02-09 00:00:00
abstract::The energy derived from optimized van der Waals interactions in closely packed, folded proteins has been proposed to be of similar energetic magnitude to hydrophobicity in stabilizing the native state. If packing is this energetically important, it should influence the evolution of protein core sequences. To test this...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011776v
更新日期:2001-12-18 00:00:00
abstract::Kynureninase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the hydrolytic cleavage of l-kynurenine to give l-alanine and anthranilic acid. beta-Benzoyl-l-alanine, the analogue of l-kynurenine lacking the aromatic amino group, was shown to a good substrate for kynureninase from Pseudomonas fluorescens, an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100955b
更新日期:2010-09-14 00:00:00
abstract::The rigor complexes that formed between rabbit skeletal muscle F-actin and chicken gizzard heavy meromyosin (HMM), in which the heavy chains had been cleaved with trypsin into 24K, 50K, and 68K fragments, were examined by using the zero-length chemical cross-linker 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC)...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00430a070
更新日期:1989-02-21 00:00:00
abstract::The role of the peripheral reaction center chlorophyll a molecule associated with His117 of the D2 polypeptide in photosystem II was investigated in Synechocystis sp. PCC 6803 using a combination of steady state, pump-probe, and picosecond time-resolved fluorescence spectroscopy. Data were obtained from intact cells a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000476v
更新日期:2000-11-21 00:00:00
abstract::Polylysine promoted extensive membrane mixing of liposomes only if the buffer pH was below the pKa of the lysyl residues. This observation suggested that fusion could be regulated in a physiological pH range if the homopolymer of L-histidine was substituted as fusogen. Microgram quantities of polyhistidine were added ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00322a001
更新日期:1985-01-01 00:00:00
abstract::The RING or Really Interesting New Gene represents a family of eukaryotic sequences that bind Zn (II) ions and participate in intracellular processes involving protein-protein interaction. Although found in over 400 different proteins, very little is known regarding the structure-function properties of these domains b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701949p
更新日期:2008-03-25 00:00:00
abstract::The electric organ of the ray, Torpedo ocellata, can serve as a source for both the acetylcholine (ACh) receptor and its ionic channel. The two entities were identified by their specific binding of [3H]ACh and [3H]perhydrohistrionicotoxin ([3H]H12-HTX), respectively. Binding of [3H]H12-HTX was inhibited by certain dru...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00618a023
更新日期:1978-12-12 00:00:00
abstract::In the minor fraction of HDL3 containing alpha-tocopherol (alphaTocOH), selective one-electron oxidation of Trp and Tyr residues of apolipoproteins A-I and A-II by *Br2- radical-anions produces the corresponding semioxidized species, TyrO* and *Trp. Repair of TyrO* by endogenous alphaTocOH generates the alpha-tocopher...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701419d
更新日期:2007-12-11 00:00:00
abstract::Human hephaestin (Hp) is a transmembrane protein that has been implicated in duodenal iron export. Mutations in the murine hephaestin gene (sla) produce microcytic, hypochromic anemia that is refractory to oral iron therapy. Hp shares approximately 50% sequence identity with the plasma multicopper ferroxidase cerulopl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051559k
更新日期:2005-11-15 00:00:00
abstract::Catalytic promiscuity is a widespread, but poorly understood, phenomenon among enzymes with particular relevance to the evolution of new functions, drug metabolism, and in vitro biocatalyst engineering. However, there is at present no way to quantitatively measure or compare this important parameter of enzyme function...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701448p
更新日期:2008-01-08 00:00:00
abstract::Cytochromes c require covalent attachment of heme via two thioether bonds at conserved CXXCH motifs, a process accomplished in prokaryotes by eight integral membrane proteins (CcmABCDEFGH), termed System I. Heme is trafficked from inside the cell to outside (via CcmABCD) and chaperoned (holoCcmE) to the cytochrome c s...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00427
更新日期:2016-06-07 00:00:00
abstract::Oxidation of the biological antioxidant alpha-tocopherol (vitamin E; TH) by peroxyl radicals yields 8a-(alkyldioxy)tocopherones, which either may hydrolyze to alpha-tocopheryl quinone (TQ) or may be reduced by ascorbic acid to regenerate TH. To define the chemistry of this putative two-electron TH redox cycle, we stud...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00451a034
更新日期:1989-12-12 00:00:00
abstract::The respiratory chain of Vibrio cholerae contains three bd-type quinol oxygen reductases as well as one cbb(3) oxygen reductase. The cbb(3) oxygen reductase has been previously isolated and characterized; however, the natural mobile electron donor(s) that shuttles electrons between the bc(1) complex and the cbb(3) oxy...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1004574
更新日期:2010-09-07 00:00:00
abstract::Neuronal PAS protein 2 (NPAS2), a heme-binding transcriptional regulatory factor, is involved in circadian rhythms. Period homologue (Per) is another important transcriptional regulatory factor that binds to cryptochrome (Cry). The resultant Per/Cry heterodimer interacts with the NPAS2/BMAL1 heterodimer to inhibit the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7023892
更新日期:2008-06-10 00:00:00
abstract::An overexpression system for spinach apocytochrome b(6) as a fusion protein to a maltose-binding protein in Escherichia coli was established using the expression vector pMalp2. The fusion of the cytochrome b(6) to the periplasmic maltose-binding protein directs the cytochrome on the Sec-dependent pathway. The cytochro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047422w
更新日期:2005-05-24 00:00:00
abstract::The photoreceptor protein rhodopsin has been reconstituted with a single phospholipid species, dimyristoylphosphatidylcholine, at a range of different lipid/protein ratios, and the exchange rate at the lipid-protein interface has been determined from the electron spin resonance spectra of spin-labeled phosphatidylchol...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00385a045
更新日期:1987-06-02 00:00:00