Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin.

Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Research Abstract Details 

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Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Abstract Text:

James C Charity,Ehud Katz,Bernard Moss,

D13 protein trimers, which form an external lattice providing curvature to the membrane of vaccinia virus immature virions, are the target of the drug rifampicin. We obtained 63 rifampicin-resistant mutants following random PCR mutagenesis of the D13L gene and 5 that arose spontaneously. Sequencing indicated that 26 mutants contained a single, unique, amino acid substitution whereas others contained 2 or more. The single mutations, including 6 previously identified, mapped to 24 different amino acids that were distributed over the length of the protein with the majority clustered between amino acids 17 to 33, 222 to 243 and 480 to 488. Two or three different substitutions occurred in six of the 24 amino acids. Representative mutant viruses of each cluster replicated to wild-type levels in the absence of rifampicin and nearly two logs higher than wild-type in the presence of drug. The large number and fitness of the mutations are remarkable in view of the extreme sequence conservation (99-100% amino acid identity amongst all orthopoxviruses). Clustering of mutations could suggest the presence of a rifampicin-binding pocket comprised of discontinuous regions of D13.

Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Publishing Authors By Initials

JC Charity,E Katz,B Moss,

For similar proteins: viral proteins research abstracts see: proteins: viral proteins research

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Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Journal Published:

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

Journal: Virology

VOLUME: 359

Page Numbers: 227-32

Journal Abbreviation: Virology

ISSN: 0042-6822

DAY: 19

MONTH: 10

YEAR: 2006

Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 110674

Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Keywords Mesh Terms:

KEYWORDS: Viral Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin. Information

Substance Name: Rifampin

Registry Number: 13292-46-1

Grant and Affiliation Information for Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin.

AFFILIATION: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Country: United States

AGENCY: United States NIAID

GRANT: Z01 AI000539-18

ACRONYM: AI

MEDLINETA: Virology

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