tailieunhanh - Báo cáo khoa học: Reaction mechanisms of thiamin diphosphate enzymes: new insights into the role of a conserved glutamate residue

Subsequent to the demonstration in the late 1950s of the catalytic power of the C2 anion⁄ylid of thiamin diphosphate, further convincing evidence was provided demonstrating that the 4¢-aminopyrimidine group plays a vital role in activation of this cofactor. | ỊFEBS Journal MINIREVIEW Reaction mechanisms of thiamin diphosphate enzymes new insights into the role of a conserved glutamate residue Boaz Shaanan and David M. Chipman Department of Life Sciences Ben-Gurion University Beer-Sheva Israel Keywords aminopyrimidine-iminopyrimidine tautomerization carboligation conserved glutamate 3D structure effective dielectric constant glyoxylate carboligase thiamin thiamin diphosphate-dependent enzyme Correspondence B. Shaanan Department of Life Sciences Ben-Gurion University Beer-Sheva 84105 Israel Fax 972 8 646 1710 Tel 972 8 647 2220 E-mail bshaanan@ D. Chipman Department of Life Sciences Ben-Gurion University Beer-Sheva 84105 Israel Fax 972 8 646 1710 Tel 972 8 647 2646 E-mail chipman@ Received 16 December 2008 revised 4 February 2009 accepted 9 February 2009 doi Subsequent to the demonstration in the late 1950s of the catalytic power of the C2 anion ylid of thiamin diphosphate further convincing evidence was provided demonstrating that the 4 -aminopyrimidine group plays a vital role in activation of this cofactor. Structural evidence from several crystal structures of thiamin diphosphate-dependent enzymes emphasized the presence of a glutamate residue in hydrogen-bonding distance from N1 as a conserved element in these enzymes. The important role of this conserved glutamate in promoting C2-H ionization and activation of thiamin diphosphate was emphasized by site-directed mutagenesis studies. This role was further elaborated by spectroscopic studies of the 4 -aminopyrimidine-imi-nopyrimidine tautomerization. The low polarity of the environment of the protein-bound thiazolium is an additional factor in the stabilization of the C2 anion ylid. The recently determined crystal structure and mutagenesis studies of glyoxylate carboligase in which the position of the conserved glutamate is occupied by valine now show that for the multi-step reaction catalyzed by this enzyme the .

• Báo cáo khoa học
• Scientific reports
• scientific research
• biochemistry
• breast cancer
• biological activities
• gastric cancer
• BMC Cancer
• Gastric cancer incidence
• Population based specialized registry
• Gastric cancer survival
• Gastric cancer clinical characteristics
• Gastric cancer pathological characteristics
• Gastroesophageal junction cancer
• Gastric cancer genomics
• Gastric cancer sequencing
• Gastric neoplasm
• D2 lymphadenectomy
• Advanced gastric cancer
• Gastric cancer surgery
• Cancer associated fibroblast
• Anti apoptosis
• Tumor cells
• Non cancerous gastric fibroblasts
• Transcription factors
• Cancer cell growth
• Potential therapeutic
• Emerging evidence
• Cancer development
• Transwell migration
• Matrigel invasion
• Cancer screening
• Discrete choice experiment
• Overall survival
• Gastric lymphoma
• Metachronous gastric adenocarcinoma
• Diffuse large B cell lymphoma
• Primary gastric lymphoma
• Diffuse gastric cancer
• Magnetic resonance imaging
• Heterogeneous enhancement
• BALB/c nude mice model
• Human originated gastric cancer cell
• Immune infiltration
• RNA seq data
• Stomach adenocarcinoma
• Tumor infiltrating immune cells
• Programmed cell death 1
• Tumor immunity
• Immune cells besides T cells
• Palliative chemotherapy
• Combination chemotherapy
• Germline mutation
• Central America
• CA 4
• Case report
• Early gastric cancer
• Splenic metastasis
• Epstein Barr virus
• Stomach cancer
• Gastric carcinoma
• Meta analysis
• Cetuximab combined
• Metastatic gastric cancer
• Identify potential biomarkers
• Target drugs
• Recurrent gastric cancer
• Traditional chemotherapy
• Mouse models
• Human gastric cancer
• Tumor formation
• Plasma membrane
• Tumor biomarkers
• Plasma membrane proteins participate
• Vascular endothelial growth factor
• 5 fluorouracil
• Single nucleotide polymorphisms
• HER2 positive recurrent
• Primary metastatic gastric cancer
• Trastuzumab based chemotherapy
• Severe postoperative complications
• Receiver operating characteristic
• Surgical gastric cancer
• Propensity score
• Adjuvant treatment
• Localized gastric cancer
• DNA sequencing
• CDH1 mutations
• Cell adhesion protein
• Mixed gastric cancer
• Metastasis associated lung adenocarcinoma transcript 1
• Cancer globally
• Non coding RNAs
• Including gastric cancer