HBV Mutation Detail Information

Virus Mutation HBV Mutation M204V


Basic Characteristics of Mutations
Mutation Site M204V
Mutation Site Sentence Analysis of the minimized structure of rtM204V HBV polymerase/3TCTP complex shows that, instead of the steric stress produced by rtV204, a loss of the van der Waals contact around the oxathiolane sugar moiety of 3TCTP caused by the mutation results in the disruption of the active site.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene P  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Hepatitis B Virus Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Lamivudine(LAM)
Location -
Literature Information
PMID 14968937
Title Mechanism of antiviral activities of 3'-substituted L-nucleosides against 3TC-resistant HBV polymerase: a molecular modelling approach
Author Chong Y,Stuyver L,Otto MJ,Schinazi RF,Chu CK
Journal Antiviral chemistry & chemotherapy
Journal Info 2003 Nov;14(6):309-19
Abstract Comparison of the active sites of the human HIV-1 reverse transcriptase (RT) and the homology-modelled hepatitis B virus (HBV) polymerase shows that the active sites of both enzymes are open to L-nucleosides, but the position where the 3'-substituent of the L-ribose projects in HBV polymerase is wider and deeper than HIV-1 RT, which enables the HBV polymerase to accommodate various 3'-substituted L-nucleosides. However, the space is not sufficient to accommodate a bulky 3'-substituent such as the 3'-azido group of L-3'-azido-3'-deoxythymidine. Analysis of the minimized structure of rtM204V HBV polymerase/3TCTP complex shows that, instead of the steric stress produced by rtV204, a loss of the van der Waals contact around the oxathiolane sugar moiety of 3TCTP caused by the mutation results in the disruption of the active site. Therefore, nucleosides, which are stabilized by additional specific interaction with the enzyme residues, can have more opportunities to circumvent the destabilization by the loss of hydrophobic interaction conferred by mutation. Specifically, the substitution at the 3'-position would be beneficial as the HBV polymerase has wide open space composed of the highly conserved motif (YMDD) where the 3'-substituents of the L-nucleosides project. As an example, our study shows that the 3'-fluorine atom contributes to the antiviral activity of L-3'-Fd4CTP against rtM204V HBV polymerase by readily compensating for the loss of the van der Waals interaction around the 2',3'-double bond through a formation of a hydrogen bond to the amide backbone of rtD205.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.