Abstract：
:Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Nonspecific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although they are thought to play a primary role in the catabolism of exogenously derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled with a clear specificity for 6-oxopurine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure of this trypanosomal NH determined to 2.5 Å resolution reveals distinctive features compared to those of both purine- and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Vandemeulebroucke A,Minici C,Bruno I,Muzzolini L,Tornaghi P,Parkin DW,Versées W,Steyaert J,Degano Mdoi
10.1021/bi100697dsubject
Has Abstractpub_date
2010-10-19 00:00:00pages
8999-9010issue
41eissn
0006-2960issn
1520-4995journal_volume
49pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:High-resolution proton nuclear magnetic resonance (1H NMR) has been used to study the conformation and dynamics of biosynthetic analogues of actinomycin D that have been substituted at one or both of the 3'-amino acids with azetidine-2-carboxylic acid, pipecolic acid, or 4-ketoproline for one or both of the prolines. ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00540a007
更新日期：1982-05-25 00:00:00
abstract：:Despite the high degree of sequence similarity in their basic-helix-loop-helix (BHLH) domains, MASH-1 and MyoD are involved in different biological processes. In order to define possible differences between the DNA binding specificities of these two proteins, we investigated the DNA binding properties of MASH-1 by cir...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00035a008
更新日期：1995-09-05 00:00:00
abstract：:HcbA1 is a unique flavoenzyme that catalyzes the first step in the bacterial hexachlorobenzene catabolic pathway. Here we report in vitro reconstitution of the HcbA1-catalyzed reaction. Detailed mechanistic studies provide evidence for nucleophilic aromatic substitution and flavin-N5-oxide formation. ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.9b00012
更新日期：2019-03-05 00:00:00
abstract：:The heme and cysteine microenvironments of bluefin tuna apomyoglobin have been investigated by examining the fluorescence properties of two extrinsic chromophores, i.e., ANS and 1,5-AEDANS. 1,5-AEDANS was covalently bound to the single cysteine residue found in the primary structure of tuna apomyoglobin. Recombination...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00531a002
更新日期：1982-01-19 00:00:00
abstract：:Gelatinase B is a matrix metalloproteinase (MMP-9) involved in tissue remodeling, development, cancer, and inflammation. Neutrophils produce three major forms of (pro)gelatinase B: 92 kDa monomers, homodimers, and complexes of gelatinase B covalently bound to neutrophil gelatinase B-associated lipocalin (NGAL). In con...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi991162e
更新日期：1999-10-19 00:00:00
abstract：:Anthrax toxin receptor 1 (ANTXR1)/tumor endothelial marker 8 (TEM8) is one of two known proteinaceous cell surface anthrax toxin receptors. A metal ion dependent adhesion site (MIDAS) present in the integrin-like inserted (I) domain of ANTXR1 mediates the binding of the anthrax toxin subunit, protective antigen (PA). ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi100887w
更新日期：2010-08-31 00:00:00
abstract：:Cytochrome c-553 from Desulfovibrio vulgaris exhibits a highly exposed heme and an unusually low reduction potential with respect to other c-type cytochromes. Solvent heme exposure has been indicated as one of the most important factors in modulating the midpoint potential of the redox center. To test this hypothesis,...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi025759x
更新日期：2002-07-09 00:00:00
abstract：:Stimulation of isolated hepatocytes with epidermal growth factor (EGF) causes rapid tyrosine phosphorylation of the EGF receptor (EGFR) and adapter/target proteins, which was monitored with 1 and 2 s resolution at 37, 20, and 4 degrees C. The temporal responses detected for multiple signaling proteins involve both tra...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi011506c
更新日期：2002-01-08 00:00:00
abstract：:The active site structures of human Q31 granzyme A, murine granzymes (A, B, C, D, E, and F), and human granzymes (A, B, and 3) isolated from cytotoxic T lymphocytes (CTL) were studied with peptide thioester substrates, peptide chloromethyl ketone, and isocoumarin inhibitors. Human Q31, murine, and human granzyme A hyd...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00222a027
更新日期：1991-02-26 00:00:00
abstract：:The functional diversity of small GTP-binding proteins (G proteins) and their ability to function as molecular switches are based on their interactions with many different proteins. A wealth of structural data has revealed that their partners are often unrelated to each other in sequence and structure, but their bindi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi049630u
更新日期：2004-06-08 00:00:00
abstract：:Myosin subfragment 1 (S1) was covalently labeled with a fluorescent dye, N-[7-(dimethylamino)-4-methyl-3-coumarinyl]maleimide (DACM), and then digested by trypsin to cleave S1 heavy chain into fragments. The DACM-labeled and trypsin-treated S1 was complexed with F-actin and treated with a zero-length cross-linker, 1-e...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00262a043
更新日期：1982-09-14 00:00:00
abstract：:Mycoplasmas are the smallest known microorganisms, with drastically reduced genome sizes. One of the essential biochemical pathways lost in mycoplasmas is methylation-mediated DNA repair (MMR), which is responsible for correction of base substitutions, insertions, and deletions in both bacteria and higher organisms. W...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi2009097
更新日期：2011-10-11 00:00:00
abstract：:We propose a simple method to find an amino acid sequence that is foldable into a globular protein with a desired structure based on a knowledge-based 3D-1D compatibility function. An asymmetric alpha-helical single-domain structure of sperm whale myoglobin consisting of 153 amino acid residues was chosen for the desi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi983006y
更新日期：1999-06-08 00:00:00
abstract：:Biological actions of insulin are initiated by activation of the insulin receptor tyrosine kinase. Protein tyrosine phosphatases (PTPases) PTP1B and PTPalpha are known to dephosphorylate the insulin receptor and may contribute to insulin resistance in diseases such as diabetes. We previously reported that overexpressi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9816103
更新日期：1999-01-05 00:00:00
abstract：:Transferred nuclear Overhauser effect measurements (in the two-dimensional mode) have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH3)4ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH3)4ATP is a competitive inhibitor with respect to MnATP ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00437a028
更新日期：1989-05-30 00:00:00
abstract：:Restrictocin and related fungal endoribonucleases from the α-sarcin family site-specifically cleave the sarcin/ricin loop (SRL) on the ribosome to inhibit translation and ultimately trigger cell death. Previous studies showed that the SRL folds into a bulged-G motif and tetraloop, with restrictocin achieving a specifi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi1018336
更新日期：2011-04-12 00:00:00
abstract：:Calcium is required for the substrate binding and for the chemical step of the interfacial catalytic turnover cycle of pancreatic phospholipase A2 (PLA2), but not for the binding of the enzyme to the interface. The role of calcium and other divalent cations (C) is analyzed for the effect on the substrate binding and k...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9728607
更新日期：1998-09-08 00:00:00
abstract：:Protein methylation is a common post-translational modification with diverse biological functions. Methyllysine reader proteins are increasingly a focus of epigenetics research and play important roles in regulating many cellular processes. These reader proteins are vital players in development, cell cycle regulation,...
journal_title：Biochemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.biochem.5b01073
更新日期：2016-03-22 00:00:00
abstract：:A pterin analogue, 5-[(3-azido-6-nitrobenzylidene)amino]-2,6-diamino-4-pyrimidinone (ANBADP), was synthesized as a probe of the pterin binding site of phenylalanine hydroxylase. The photoaffinity label has been found to be a competitive inhibitor of the enzyme with respect to 6,7-dimethyltetrahydropterin, having a Ki ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00241a024
更新日期：1991-07-09 00:00:00
abstract：:This paper provides further characterization of a receptor that, in cells lacking the LDL receptor (FH fibroblasts), mediates lipoprotein binding, uptake, and degradation when incubated with oleate at concentrations not exceeding albumin binding capacity. This oleate-activated receptor is genetically distinct from the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00171a017
更新日期：1994-02-08 00:00:00
abstract：:Histidine-containing protein, HPr, is a phosphocarrier protein that is part of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated by enzyme I, and P-HPr transfers the phosphoryl group to the IIA domain of a number of sugar-specific enzyme II complexes. Autocatalytic phosphoryl tra...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00073a025
更新日期：1993-06-08 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
abstract：:DNA-DNA interstrand cross-links are thought to be important for the cytotoxicity of many chemotherapeutic agents. To study this more definitively, adduct site-specific methods are used to construct a plasmid with a single nitrogen mustard interstrand cross-link (inter-HN2-pTZSV28). Replication efficiency (RE = [coloni...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi962778w
更新日期：1997-03-25 00:00:00
abstract：:A gentle and rapid isolation procedure is described yielding fractions containing better than 95% pure OmpF porin of Escherichia coli BE with different amounts of bound lipopolysaccharide (LPS). The procedure employs continuous free-flow electrophoresis (FFE) in the presence of detergent above its critical micelle con...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00436a010
更新日期：1989-05-16 00:00:00
abstract：:The subtilisins have an extended substrate binding cleft comprising at least 8 subsites. Two pockets at the S1 and S4 sites are particularly conspicuous, and the interactions between substrate and these two pockets are very important for the substrate specificity. Phe residues have mutationally been introduced at one ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00062a016
更新日期：1993-03-23 00:00:00
abstract：:Segregation of mRNAs in the cytoplasm of polar cells has been demonstrated for proteins involved in Xenopus and Drosophila oogenesis, and for some proteins in somatic cells. It is assumed that vectorial transport of the messages is generally responsible for this localization. The mRNA encoding the basic protein of cen...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9800247
更新日期：1998-05-12 00:00:00
abstract：:Preferential interaction of trans-membrane alpha-helices whose hydrophobic length matches the hydrophobic thickness of the lipid bilayer could be a mechanism of retention in the Golgi apparatus. We have used fluorescence methods to study the interaction of peptides Ac-K2-G-Lm-W-Ln-K2-A-amide (Pm+n) with bilayers of ph...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi972441+
更新日期：1998-01-13 00:00:00
abstract：:Typical of many transcriptional regulatory proteins, the lambdoid bacteriophage repressors bind cooperatively to multiple sites on DNA. This cooperative binding is essential for establishment and maintenance of phage lysogeny. In the phage, two repressor homodimers, one bound at each of the adjacent operator sites, in...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi027318j
更新日期：2003-04-15 00:00:00
abstract：:The thermotropic behavior and molecular properties of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-dihydrosterculoyl-sn-glycero-3-phosphoethanolamine (PDSPE) have been investigated by 2H NMR spectroscopy using samples selectively labeled at the 5'-, 9'-, 10'-, and 16'-positions of the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00325a038
更新日期：1985-02-12 00:00:00
abstract：:Typical cytochrome P450s secure the heme prosthetic group with a cysteine thiolate ligand bound to the iron, electrostatic interactions with the heme propionate carboxylates, and hydrophobic interactions with the heme periphery. In addition to these interactions, CYP4B1 covalently binds heme through a monoester link f...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi051267j
更新日期：2005-10-25 00:00:00
