Abstract:
:The enzyme PvdQ (E.C. 3.5.1.97) from Pseudomonas aeruginosa is an N-terminal nucleophile hydrolase that catalyzes the removal of an N-myristyl substituent from a biosynthetic precursor of the iron-chelating siderophore pyoverdine. Inhibitors of pyoverdine biosynthesis are potential antibiotics since iron is essential for growth and scarce in most infections. PvdQ also catalyzes hydrolytic amide bond cleavage of selected N-acyl-l-homoserine lactone quorum-sensing signals used by some Gram-negative pathogens to coordinate the transcription of virulence factors. The resulting quorum-quenching activity of PvdQ has potential applications in antivirulence therapies. To inform both inhibitor design and enzyme engineering efforts, a series of n-alkylboronic acid inhibitors of PvdQ was characterized to reveal determinants of ligand selectivity. A simple homologation series results in compounds with Ki values that span from 4.7 mM to 190 pM, with a dependence of ΔGbind values on chain length of -1.0 kcal/mol/CH2. X-ray crystal structures are determined for the PvdQ complexes with 1-ethyl-, 1-butyl-, 1-hexyl-, and 1-octylboronic acids at 1.6, 1.8, 2.0, and 2.1 Å resolution, respectively. The 1-hexyl- and 1-octylboronic acids form tetrahedral adducts with the active-site N-terminal Ser217 in the β-subunit of PvdQ, and the n-alkyl substituents are bound in the acyl-group binding site. The 1-ethyl- and 1-butylboronic acids also form adducts with Ser217 but instead form trigonal planar adducts and extend their n-alkyl substituents into an alternative binding site. These results are interpreted to propose a ligand discrimination model for PvdQ that informs the development of PvdQ-related tools and therapeutics.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Clevenger KD,Wu R,Liu D,Fast Wdoi
10.1021/bi501086ssubject
Has Abstractpub_date
2014-10-28 00:00:00pages
6679-86issue
42eissn
0006-2960issn
1520-4995journal_volume
53pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats is destroyed by propyne in a reduced nicotinamide adenine dinucleotide dependent process which also results in vivo in the accumulation of an abnormal green porphyrin. The green porphyrin has been identified by its electronic absorption, mass spect...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00528a033
更新日期:1981-12-08 00:00:00
abstract::Chemical modification of Torpedo californica acetylcholinesterase by various sulfhydryl reagents results in its conversion to one of two principal states. One of these states, viz., that produced by disulfides and alkylating agents, is stable. The second state, produced by mercury derivatives, is metastable. At room t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00252a006
更新日期:1994-12-06 00:00:00
abstract::By exposing photosystem II (PSII) samples to an incrementing number of excitation flashes at room temperature, followed by freezing, we could compare the Mn-derived multiline EPR signal from the S2 oxidation state as prepared by 1, 5, 10, and 25 flashes of light. While the S2 multiline signals exhibited by these sampl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026848c
更新日期:2003-03-11 00:00:00
abstract::The chromatin-associated high-mobility group (HMG) proteins of the plant HMGB family are characterized by a central HMG-box domain that is flanked by a basic N-terminal and an acidic C-terminal domain. By functional interaction with certain transcription factors, HMGB proteins contribute to transcriptional regulation....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi6024947
更新日期:2007-05-29 00:00:00
abstract::The thermodynamic and activation parameters for the reduction of delta 1-pyrroline-2-carboxylic acid (an alpha-imino acid) by reduced nicotinamide adenine dinucleotide phosphate (NADPH) are compared with those for the reduction of the same imino acid by the glutamate dehydrogenase-NADPH complex. The enthalpies of acti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00341a013
更新日期:1985-09-24 00:00:00
abstract::The calcitonin/CGRP gene pre-mRNA is alternatively spliced in a tissue-specific manner resulting in the formation of calcitonin mRNA in thyroid C-cells and CGRP mRNA in neurons. Computer analysis of the RNA containing the 3' splice acceptor of the calcitonin-specific exon 4 predicts that this region has the potential ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9808058
更新日期:1998-11-10 00:00:00
abstract::Proteolytic degradation of glutamine synthetase (GS) in Escherichia coli is known to follow "marking" by oxidative modification. At an early stage of the degradative pathway, oxidation of His 269 and Arg 344 abolishes GS enzymatic activity. We propose a mechanism for the early stage of oxidative inactivation of GS on ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00082a022
更新日期:1993-08-10 00:00:00
abstract::High-molecular mass thioredoxin reductases (TRs) are pyridine nucleotide disulfide oxidoreductases that catalyze the reduction of the disulfide bond of thioredoxin (Trx). Trx is responsible for reducing multiple protein disulfide targets in the cell. TRs utilize reduced β-nicotinamide adenine dinucleotide phosphate to...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400931k
更新日期:2014-01-28 00:00:00
abstract::We have determined the nucleotide sequence and the derived amino acid sequence of the phosphoprotein-encoding region of the chicken vitellogenin III gene. The sequence of this minor vitellogenin could be aligned with exon 22 up to exon 27 of the previously sequenced major vitellogenin II gene (van het Schip et al., 19...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00432a034
更新日期:1989-03-21 00:00:00
abstract::S100 beta is a calcium-binding protein, which regulates the activities of several enzymes and inhibits the phosphorylation of a variety of protein kinase C substrates in a calcium-dependent manner. The protein was recently found to activate a retinal membrane guanylate cyclase, and in this paper, we report that it inh...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9802115
更新日期:1998-07-28 00:00:00
abstract::Liver alcohol dehydrogenase (LADH) carboxymethylated at Cys-46 (CMLADH) forms two different ternary complexes with 4-trans-(N,N-dimethylamino)cinnamaldehyde (DACA). The complex with reduced nicotinamide adenine dinucleotide (NADH) is characterized by a 38-nm red shift of the long-wavelength pi, pi* transition to 436 n...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00321a085
更新日期:1984-12-18 00:00:00
abstract::Epitranscriptomic RNA modifications can serve as recognition elements for the recruitment of effector proteins (i.e., "readers") to modified transcripts. While these interactions play an important role in mRNA regulation, there is a major gap in our understanding of the sequence determinants critical for the binding o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00485
更新日期:2019-08-06 00:00:00
abstract::Thermal transitions of type I collagen fibrils were investigated by differential scanning calorimetry and spectrophotometry of turbidity within a wide range of external conditions. The advanced microcalorimeter allowed us to carry out the measurements at low concentrations of collagen (0.15-0.3 mg/mL). At these concen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980360n
更新日期:1998-06-02 00:00:00
abstract::Proteorhodopsins are a recently discovered class of microbial rhodopsins, ubiquitous in marine bacteria. Over 4000 variants have thus far been discovered, distributed throughout the oceans of the world. Most variants fall into one of two major groups, green- or blue-absorbing proteorhodopsin (GPR and BPR, respectively...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7018964
更新日期:2008-03-18 00:00:00
abstract::From the larger set of 191 variants at all the variable contact positions in the turkey ovomucoid third domain, we selected a subset that consists of Asp, Glu, His, and Lys residues at eight of the nine contiguous P6-P3' positions (residues 13-21), the exception being P3-Cys16 which is involved in a conserved disulfid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0269512
更新日期:2003-03-18 00:00:00
abstract::Polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) subunits can bind in the minor groove of DNA at predetermined sequences with subnanomolar affinity and high specificity. Covalent linkage of polymer subunits using a gamma-aminobutyric acid linker has been shown to increase both the affinity and sp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0022339
更新日期:2001-01-09 00:00:00
abstract::The steady-state tryptophan fluorescence and time-resolved tryptophan fluorescence of Escherichia coli thioredoxin, calf thymus thioredoxin, and yeast thioredoxin have been studied. In all proteins, the tryptophan residues undergo strong static and dynamic quenching, probably due to charge-transfer interactions with t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00434a038
更新日期:1989-04-18 00:00:00
abstract::The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide modifi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00002a001
更新日期:1995-01-17 00:00:00
abstract::Hydrogenase from Chromatium vinosum contains 1 Ni, 11-12 Fe, and ca. 9 sulfides. EPR and Mössbauer studies of the enzyme prepared in four different oxidation states show that the enzyme contains two Fe4S4 and one Fe3S4 cluster. In the oxidized (2+) state, the Mössbauer parameters of the two Fe4S4 clusters are typical ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00182a029
更新日期:1994-04-26 00:00:00
abstract::Methylated DNA binding protein 2 (MeCP2) is a methyl CpG binding protein whose key role is the recognition of epigenetic information encoded in DNA methylation patterns. Mutation or misregulation of MeCP2 function leads to Rett syndrome as well as a variety of other autism spectrum disorders. Here, we have analyzed in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9019753
更新日期:2010-05-25 00:00:00
abstract::O6-Alkylguanine-DNA alkyltransferase (AGT) is an important cellular defense against the mutagenic effects of DNA alkylating agents. In humans this defense can contribute to the ability of some tumors to resist the effects of chemotherapeutic agents that act through DNA alkylation. We report here studies that character...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960971k
更新日期:1996-12-03 00:00:00
abstract::Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first ste...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01282
更新日期:2016-04-05 00:00:00
abstract::Aminoacyl-tRNA synthetases contain one or three Mg(2+) ions in their catalytic sites. In addition to their role in ATP binding, these ions are presumed to play a role in catalysis by increasing the electropositivity of the alpha-phosphate and stabilizing the pentavalent transition state. In the class II aaRS, two high...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049617+
更新日期:2004-06-08 00:00:00
abstract::Two antisera used in the radioimmunoassay for human fibrinopeptide A (FPA) which appear to have different immunochemical specificities have been tested for cross-reactivity with fibrinogen and with three fragments of fibrinogen which contain the FPA sequence. These fragments were the three-chain, NH2-terminal disulfid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00651a004
更新日期:1976-03-23 00:00:00
abstract::Reaction of 1-oxiranylpyrene (1-OP) with DNA and the structures of the covalent and noncovalent complexes formed were studied in aqueous media (5 mM phosphate buffer with 0.1 M NaCl, pH 7) by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy in order to gain an understanding of pos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00318a009
更新日期:1984-11-06 00:00:00
abstract::Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exempli...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7018578
更新日期:2008-02-05 00:00:00
abstract::A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi5011317
更新日期:2014-12-09 00:00:00
abstract::Heparin decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor as a result of its strong binding to the enzyme. Here, we used the slow-binding kinetic approach to decide whether the enzyme-inhibitor interaction proceeds via a two-step mechanism and to identify the step that is affected...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00086a031
更新日期:1993-09-07 00:00:00
abstract::Reporter gene transactivation by human p53 is inhibited in budding yeast lacking the TRR1 gene encoding thioredoxin reductase. To investigate the role of thioredoxin in controlling p53 activity, the level of reporter gene transactivation by p53 was determined in yeast lacking the TRX1 and TRX2 genes encoding cytosolic...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900757q
更新日期:2009-09-29 00:00:00
abstract::Ppr from the purple phototrophic bacterium, Rhodospirillum centenum (also known as Rhodocista centenaria), is a hybrid of photoactive yellow protein (PYP), bacteriophytochrome (Bph), and histidine kinase (HK) domains. The holo-Ppr (containing both chromophores) exhibits characteristic absorption maxima at 435 nm due t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700616j
更新日期:2007-07-17 00:00:00