1C2P

HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE

Summary for 1C2P

• Entry DOI: 10.2210/pdb1c2p/pdb
• Descriptor: RNA-DEPENDENT RNA POLYMERASE (2 entities in total)
• Functional Keywords: polymerase rna-dependent rna polymerase hepatitis c virus ns5b apoenzyme, transferase
• Biological source: Hepatitis C virus
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : P26663
• Total number of polymer chains: 2
• Total formula weight: 129058.34

Authors

Lesburg, C.A.,Cable, M.B.,Ferrari, E.,Hong, Z.,Mannarino, A.F.,Weber, P.C. (deposition date: 1999-07-26, release date: 2000-04-05, Last modification date: 2024-10-09)

Primary citation

Lesburg, C.A.,Cable, M.B.,Ferrari, E.,Hong, Z.,Mannarino, A.F.,Weber, P.C.
Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site.
Nat.Struct.Biol., 6:937-943, 1999

PubMed Abstract: Various classes of nucleotidyl polymerases with different transcriptional roles contain a conserved core structure. Less is known, however, about the distinguishing features of these enzymes, particularly those of the RNA-dependent RNA polymerase class. The 1. 9 A resolution crystal structure of hepatitis C virus (HCV) nonstructural protein 5B (NS5B) presented here provides the first complete and detailed view of an RNA-dependent RNA polymerase. While canonical polymerase features exist in the structure, NS5B adopts a unique shape due to extensive interactions between the fingers and thumb polymerase subdomains that serve to encircle the enzyme active site. Several insertions in the fingers subdomain account for intersubdomain linkages that include two extended loops and a pair of antiparallel alpha-helices. The HCV NS5B apoenzyme structure reported here can accommodate a template:primer duplex without global conformational changes, supporting the hypothesis that this structure is essentially preserved during the reaction pathway. This NS5B template:primer model also allows identification of a new structural motif involved in stabilizing the nascent base pair.

PubMed: 10504728
DOI: 10.1038/13305

Experimental method

X-RAY DIFFRACTION (1.9 Å)