Abstract:
:α-Isopropylmalate synthase (α-IPMS) is a multi-domain protein catalysing the condensation of α-ketoisovalerate (α-KIV) and acetyl coenzyme A (AcCoA) to form α-isopropylmalate. This reaction is the first committed step in the leucine biosynthetic pathway in bacteria and plants, and α-IPMS is allosterically regulated by this amino acid. Existing crystal structures of α-IPMS from Mycobacterium tuberculosis (MtuIPMS) indicate that this enzyme has a strikingly different domain arrangement in each monomer of the homodimeric protein. This asymmetry results in two distinct interfaces between the N-terminal catalytic domains and the C-terminal regulatory domains in the dimer. In this study, residues Arg97 and Asp444 across one of these unequal domain interfaces were substituted to evaluate the importance of protein asymmetry and salt bridge formation between this pair of residues. Analysis of solution-phase structures of wild-type and variant MtuIPMS indicates that substitutions of these residues have little effect on overall protein conformation, a result also observed for addition of the feedback inhibitor leucine to the wild-type enzyme. All variants had increased catalytic efficiency relative to wild-type MtuIPMS, and those with an Asp444 substitution displayed increased affinity for the substrate AcCoA. All variants also showed reduced sensitivity to leucine and altered biphasic reaction kinetics when compared with those of the wild-type enzyme. It is proposed that substituting residues at the asymmetric domain interface increases flexibility in the protein, particularly affecting the AcCoA binding site and the response to leucine, without penalty on catalysis.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Huisman FH,Squire CJ,Parker EJdoi
10.1016/j.bbrc.2013.02.092subject
Has Abstractpub_date
2013-04-05 00:00:00pages
249-54issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(13)00377-Xjournal_volume
433pub_type
杂志文章abstract::Temozolomide (TMZ) is a methylating agent used in chemotherapy against glioblastoma. This work was designed to clarify details in repair pathways acting to remove DNA double-strand breaks (DSBs) induced by TMZ. Cultured mouse embryonic fibroblasts were used which were deficient in DSB repair genes such as homologous r...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2009.07.045
更新日期:2009-10-02 00:00:00
abstract::We have sequenced all mitochondrial tRNA genes from a patient with chronic progressive external ophthalmoplegia (CPEO) and mitochondrial myopathy, who had no detectable large mtDNA deletions. Direct sequencing failed to detect previously reported mutations and showed a heteroplasmic mutation at nucleotide 12,276 in th...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2004.11.170
更新日期:2005-02-18 00:00:00
abstract::Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding plant lectin, has recently drawn a rising attention for cancer biologists because PCL bears remarkable anti-tumor activities and thus inducing programmed cell death (PCD) including apoptosis and autophagy in cancer cells. In this review, we focus on exp...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章,评审
doi:10.1016/j.bbrc.2011.02.049
更新日期:2011-03-25 00:00:00
abstract::The pH dependence of the behavior of chicken liver xanthine dehydrogenase in the course of reductive titrations with sodium dithionite has been examined. Below pH 8.5, the behavior of xanthine dehydrogenase is similar to that of the much better understood milk xanthine oxidase, with the amount of neutral semiquinone a...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1993.1934
更新日期:1993-08-16 00:00:00
abstract::We prepared three peptide fragments (fg.59-105, fg.63-105 and fg.64-105) by the BrCN cleavage of mutant lysozymes where Ile58, Trp62 and Trp63 were mutated to Met, respectively. From the analysis of formation of the disulfide bonds among Cys64, Cys76, Cys80 and Cys94 in the renaturation of each peptide fragment from t...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1996.1640
更新日期:1996-11-01 00:00:00
abstract::We have previously identified the region containing transcriptional enhancer in mouse immunoglobulin heavy chain (IgH) gene as an initiation region of DNA replication. The octamer sequence therein has been found to be essential for initiation of DNA replication as well as for transcription. Octamer-binding protein fam...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.1593
更新日期:1994-05-16 00:00:00
abstract::Interleukin 12 has demonstrated a wide spectrum of bioactivity on T and NK cells both in vitro and in vivo. Therapeutic potential of these activities has been suggested by studies in murine tumor, viral and microbial models of disease. We have investigated the in vivo effect of rhlL-12 in cynomolgus monkeys treated wi...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.2583
更新日期:1994-11-15 00:00:00
abstract::Glycogen-storage disease type II (GSD II, acid maltase deficiency, Pompe's disease) is caused by defects in the lysosomal acid alpha-glucosidase (GAA) gene. Clinically, patients with the severe infantile form of GSD II have muscle weakness and cardiomyopathy eventually leading to death before the age of two years. Pat...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1997.6749
更新日期:1997-06-09 00:00:00
abstract::The mechanism(s) involved in the generation of free radicals in human leukocytes by phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMP), lipopolysaccharide (LPS), arachidonic acid (AA), and recombinant-tumor necrosis factor-1-alpha (r-TNF-1 alpha) was investigated. Calmodulin antagonists, chlo...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(90)90626-x
更新日期:1990-03-30 00:00:00
abstract::Cultured endothelial cells release a potent vasoconstrictor peptide, endothelin. Cumulative addition of synthetic endothelin to isolated rabbit aortic rings elicited a concentration-dependent increase in contractile tension which was endothelium-independent. In cultured rabbit vascular smooth muscle cells loaded with ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(89)80180-9
更新日期:1989-01-16 00:00:00
abstract::An increase in plasma prorenin during pregnancy suggests that prorenin might be synthesized in the ovary and the secretion of renin or prorenin may be stimulated by an ovarian steroid-mediated process. Recently, renin and angiotensinogen have been identified in human ovarian follicular fluid. However, there is conside...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(87)90466-9
更新日期:1987-01-15 00:00:00
abstract::Rat mast cell protease of type 1 (RMCP1) is a specific marker of connective tissue mast cells selectively occurring in some tissues, e.g., the tongue. Its amino acid sequence is known (Le Trong et al., Biochem. 1987, 26, 6988-6994) but not the corresponding nucleotide sequence. Amplification of mRNAs from rat tongue w...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.1270
更新日期:1994-03-15 00:00:00
abstract::This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2010.04.050
更新日期:2010-04-10 00:00:00
abstract::Peptidylarginine deiminases (PADs) convert arginine residues in proteins into citrulline residues Ca(2+)-dependently. PAD V was recently found in granulocyte-differentiated HL-60 cells. To find a target of PAD V, we incubated HL-60 granulocytes with the calcium ionophore A23187 and studied deiminated proteins by immun...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.6303
更新日期:2002-01-25 00:00:00
abstract::The tetracycline-regulated gene expression system has been widely used in mice to turn a transgene on and off in a target organ, but with only limited success. We developed an advanced system in which a Tet-off regulation unit was integrated into the ROSA26 locus and became active after Cre-mediated excision of the ne...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.10.054
更新日期:2005-12-16 00:00:00
abstract::Oxidized low-density lipoproteins (LDL) accumulate in the vascular wall and promote a local inflammatory process contributing to the progression of atheromatous plaque. The key role of myeloperoxidase (MPO) in this process has been documented and the enzyme has been involved in the oxidative modification of apolipopro...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.09.013
更新日期:2005-11-11 00:00:00
abstract::Antithrombin inhibits chemokine-induced migration of neutrophils by activating heparan sulfate proteoglycan-dependent signaling. Mechanisms of antithrombin's effects on neutrophils were, therefore, studied by testing function and expression of heparan sulfate proteoglycans in RT-PCR or flow cytometry and cell migratio...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.5534
更新日期:2001-09-14 00:00:00
abstract::Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflam...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2016.04.010
更新日期:2016-05-13 00:00:00
abstract::A few decades ago, researchers found emerging evidence showing that a number of sequential events lead to the pathological cascade of Alzheimer's disease (AD) which is caused by the accumulation of amyloid beta (Aβ), a physiological peptide, in the brain. Therefore, regulation of Aβ represents a crucial treatment appr...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2016.06.103
更新日期:2016-09-02 00:00:00
abstract::To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the re...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(92)91552-2
更新日期:1992-11-30 00:00:00
abstract::Tissue-engineered grafts for tissue regeneration include either mature or progenitor cells seeded onto biomatrices that provide shape and support for developing tissue. Popular biomaterials used in orthopaedic surgery include collagen type I, hyaluronic acid, hydroxyapatite, and polylactic polyglycolic acid (PLGA). Bi...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2004.06.165
更新日期:2004-08-20 00:00:00
abstract::Genomic DNA of the phytopathogenic Erwinia chrysanthemi PY35 was partially digested with Sau3AI, ligated into the BamHI site of pBluescript II SK+, and introduced into E. coli. One clone that was able to hydrolyse carboxymethylcellulose and polygalacturonic acid was selected. A 2.9 kb fragment containing the pelL1 gen...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2000.2137
更新日期:2000-02-16 00:00:00
abstract::Two species of scarab beetles, the Osaka beetle (Anomala osakana) and the Japanese beetle (Popillia japonica), utilize the opposite enantiomers of japonilure, (Z)-5-(1-decenyl)oxacyclopentan-2-one, as their sex pheromones. Each species produces only one of the enantiomers that functions as its own sex pheromone and as...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.9278
更新日期:1998-09-18 00:00:00
abstract::Cells of the monocyte series respond to follicle stimulating hormone (FSH) by poorly characterized mechanisms. We studied FSH-receptors (FSH-R) and FSH response in nontransformed human monocytes and in osteoclasts differentiated from these cells. Western blot and PCR confirmed FSH-R expression on monocytes or osteocla...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2010.02.112
更新日期:2010-03-26 00:00:00
abstract::1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] initiates the hydrolysis of sphingomyelin in ROS 17/2.8 osteosarcoma cells with the resultant generation of cell-associated ceramide. Increases in ceramide levels were detectable at 15 min and maximal one hour after exposure of cells to 1,25(OH)(2)D(3). Neither 1,25(OH)(2)D...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2000.2905
更新日期:2000-06-24 00:00:00
abstract::The cardiotoxin analogue III (CTX III), isolated from the Taiwan Cobra venom (Naja naja atra), is a sixty amino acid, all beta-sheet protein. The 2,2,2-trifluoro ethanol (TFE) induced unfolding of CTX III is studied under acidic conditions (pH 2.5). Using circular dichroism, 1-anilino-8-napthalene sulphonic acid bindi...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.1221
更新日期:1995-02-15 00:00:00
abstract::Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by cl...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.08.104
更新日期:2012-09-28 00:00:00
abstract::Pancreatic carcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The regulatory mechanisms for the rapid proliferation of pancreatic cancer cells and the particular aggressiveness of this cancer are still not fully understood. In mammalian cells, three MAPK families including ERK...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.4595
更新日期:2001-03-30 00:00:00
abstract::SHPS-1 (SHP substrate-1) is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites, in its cytoplasmic region. Various mitogens and cell adhesion induce tyrosine...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1996.6047
更新日期:1997-02-03 00:00:00
abstract::Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer includi...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2016.05.153
更新日期:2016-08-05 00:00:00