HBV Mutation Detail Information

Virus Mutation HBV Mutation M204I


Basic Characteristics of Mutations
Mutation Site M204I
Mutation Site Sentence In this regard;homology modeled structure of HBV polymerase were used for minimization;conformational search and induced fit docking followed by binding energy calculation on wild type as well as on mutant-HBV polymerases (L180M;M204V;M204I;L180M+M204V;L180M-M204I).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region P
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 18765256
Title Understanding the molecular basis of HBV drug resistance by molecular modeling
Author Sharon A,Chu CK
Journal Antiviral research
Journal Info 2008 Dec;80(3):339-53
Abstract Despite the significant successes in the area of anti-HBV agents, resistance and cross-resistance against available therapeutics are the major hurdles in drug discovery. The present investigation is to understand the molecular basis of drug resistance conferred by the B and C domain mutations of HBV-polymerase on the binding affinity of five anti-HBV agents [lamivudine (3TC, 1), adefovir (ADV, 2), entecavir (ETV, 3), telbivudine (LdT, 4) and clevudine (l-FMAU, 5)]. In this regard, homology modeled structure of HBV-polymerase was used for minimization, conformational search and induced fit docking followed by binding energy calculation on wild-type as well as on mutant HBV-polymerases (L180M, M204V, M204I, L180M+M204V, L180M-M204I). Our studies suggest a significant correlation between the fold resistances and the binding affinity of anti-HBV nucleosides. The binding mode studies reveals that the domain C residue M204 is closely associated with sugar/pseudosugar ring positioning in the active site. The positioning of oxathiolane ring of 3TC (1) is plausible due the induced fit orientation of the M204 residue in wild-type, and further mutation of M204 to V204 or I204 reduces the final binding affinity which leads to the drug resistance. The domain B residue L180 is not directly close ( approximately 6A) to the nucleoside/nucleoside analogs, but indirectly associated with other active-site hydrophobic residues such as A87, F88, P177 and M204. These five hydrophobic residues can directly affect on the incoming nucleoside analogs in terms of its association and interaction that can alter the final binding affinity. There was no sugar ring shifting observed in the case of adefovir (2) and entecavir (3), and the position of sugar ring of 2 and 3 is found similar to the sugar position of natural substrate dATP and dGTP, respectively. The exocyclic double bond of entecavir (3) occupied in the backside hydrophobic pocket (made by residues A87, F88, P177, L180 and M204), which enhances the overall binding affinity. The active site binding of LdT (4) and l-FMAU (5) showed backward shifting along with upward movement without enforcing M204 residue and this significant different binding mode makes these molecules as polymerase inhibitors, without being incorporated into the growing HBV-DNA chain. Structural results conferred by these l- and d-nucleosides, explored the molecular basis of drug resistance which can be utilized for future anti-HBV drug discovery.
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.