The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity.

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Abstract Text:

William C Drosopoulos,Vinayaka R Prasad,

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, contains conserved motifs common to retroviral reverse transcriptases and telomerases. Within the C motif of hTERT is the Leu866-Val867-Asp868-Asp869 tetrapeptide that includes a catalytically essential aspartate dyad. Site-directed mutagenesis of Tyr183 and Met184 residues in HIV-1 RT, residues analogous to Leu866 and Val867, revealed that they are key determinants of nucleotide binding, processivity and fidelity. In this study, we show that substitutions at Val867 lead to significant changes in overall enzyme activity and telomere repeat extension rate, but have little effect on polymerase processivity. All Val867 substitutions examined (Ala, Met, Thr) led to reduced repeat extension rates, ranging from approximately 20 to 50% of the wild-type rate. Reconstitution of V867M hTERT and telomerase RNAs (TRs) with mutated template sequences revealed the effect on extension rate was associated with a template copying defect specific to template A residues. Furthermore, the Val867 hTERT mutants also displayed increased nucleotide incorporation fidelity, implicating Val867 as a determinant of telomerase fidelity. These findings suggest that by evolving to have a valine at position 867, the wild-type hTERT protein may have partially compromised polymerase fidelity for optimal and rapid repeat synthesis.

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Publishing Authors By Initials

WC Drosopoulos,VR Prasad,

For similar amino acids, peptides, and proteins: amino acids: amino acids, branched-chain: valine research abstracts see: amino acids, peptides, and proteins: amino acids: amino acids, branched-chain: valine research

PUBMED ID PMID:

MEDLINE DATE:

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Nucleic acids research

VOLUME: 35

Page Numbers: 1155-68

Journal Abbreviation: Nucleic Acids Res.

ISSN: 1362-4962

DAY: 30

MONTH: 01

YEAR: 2007

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 411011

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Keywords Mesh Terms:

KEYWORDS: Valine

MESH TERMS: genetics

Chemical & Substance for Abstract: The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Information

Substance Name: Telomerase

Registry Number: EC 2.7.7.49

Grant and Affiliation Information for The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity.

AFFILIATION: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. drosopou@aecom.yu.edu

Country: England

AGENCY: United States NIAID

GRANT: R01 AI030861

ACRONYM: AI

MEDLINETA: Nucleic Acids Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity Related Publications

• A Theoretical Math Model for Projecting AIS3+ Thoracic Injury for Belted Occupants in Frontal Impact.
• A new mutation in exon 3 of the SCL39A4 gene in a Tunisian family with severe acrodermatitis enteropathica.
• A new preference-based analysis for randomized trials can estimate treatment acceptability and effect in compliant patients.
• A simple and efficient method for the purification of seminal plasmin, an antimicrobial protein from bovine seminal plasma.
• Alpha tocopheryl succinate inhibits melanocyte-stimulating hormone (MSH)-sensitive adenylate cyclase activity in melanoma cells.
• Alpha tocopheryl succinate, retinoic acid and polar carotenoids enhanced the growth-inhibitory effect of a cholesterol-lowering drug on immortalized and transformed nerve cells in culture.
• Biomechanical Analysis of Human Abdominal Impact Responses and Injuries through Finite Element Simulations of a Full Human Body Model.
• Combined effect of adenosine 3',5'-cyclic monophosphate stimulating agents, vitamin E succinate, and heat on the survival of murine B-16 melanoma cells in culture.
• Cryoelectron microscopy structures of rotavirus NSP2-NSP5 and NSP2-RNA complexes: implications for genome replication.
• D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells.
• Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture.
• Effect of alpha tocopheryl succinate on cyclic AMP-dependent protein kinase activity in murine B-16 melanoma cells in culture.
• Effect of hyperthermia in combination with vitamin E and cyclic AMP on neuroblastoma cells in culture.
• Effects of dl-alpha-tocopheryl succinate in combination with sodium butyrate and cAMP stimulating agent on neuroblastoma cells in culture.
• Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner.
• Improved neck injury risk curves for tension and extension moment measurements of crash dummies.
• Induction of autolysis in starved Escherichia coli cells by seminalplasmin, an antimicrobial protein from bovine seminal plasma.
• Induction of differentiated phenotypes in melanoma cells by a combination of an adenosine 3',5'-cyclic monophosphate stimulating agent and D-alpha tocopheryl succinate.
• Innovations in integrative healthcare education: the AMSA CAM education projects and the University of New Mexico Integrative Medicine Program.
• New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug.
• Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy.
• Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells.
• Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy.
• Regulation of the Expression of Tropomyosins and Actin Cytoskeleton by ras Transformation.
• Seminalplasmin, an antimicrobial protein from bovine seminal plasma, inhibits peptidoglycan synthesis in Escherichia coli.
• Study on the specificity of alpha-tocopheryl (vitamin E) acid succinate effects on melanoma, glioma and neuroblastoma cells in culture.
• The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity.
• Vitamin E (d-alpha-tocopheryl succinate) decreases mitotic accumulation in gamma-irradiated human tumor, but not in normal, cells.
• Zinc: mechanisms of host defense.
• dl-alpha-Tocopheryl succinate enhances the effect of gamma-irradiation on neuroblastoma cells in culture.