1N5Y

HIV-1 Reverse Transcriptase Crosslinked to Post-Translocation AZTMP-Terminated DNA (Complex P)

Summary for 1N5Y

• Entry DOI: 10.2210/pdb1n5y/pdb
• Related: 1HYS 1RTD 2HMI
• Descriptor: 5'-D(*AP*TP*GP*C*TP*AP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3', 5'-D(*A*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*(ATM))-3', REVERSE TRANSCRIPTASE, ... (7 entities in total)
• Functional Keywords: hiv, translocation, nucleotide excision, drug resistance, complex p, transferase-immune system-dna complex, transferase/immune system/dna
• Biological source: Human immunodeficiency virus 1; More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03366 P03366
• Total number of polymer chains: 6
• Total formula weight: 176776.84

Authors

Sarafianos, S.G.,Clark Jr., A.D.,Das, K.,Tuske, S.,Birktoft, J.J.,Ilankumaran, P.,Ramesha, A.R.,Sayer, J.M.,Jerina, D.M.,Boyer, P.L.,Hughes, S.H.,Arnold, E. (deposition date: 2002-11-07, release date: 2003-01-28, Last modification date: 2024-10-30)

Primary citation

Sarafianos, S.G.,Clark Jr., A.D.,Das, K.,Tuske, S.,Birktoft, J.J.,Ilankumaran, P.,Ramesha, A.R.,Sayer, J.M.,Jerina, D.M.,Boyer, P.L.,Hughes, S.H.,Arnold, E.
Structure of HIV-1 Reverse Transcriptase with Pre-Translocation and Post-Translocation AZTMP-Terminated DNA
Embo J., 21:6614-6624, 2002

PubMed Abstract: AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the nucleotide-binding site (pre-translocation complex N) but not at the 'priming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 A resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation.

PubMed: 12456667
DOI: 10.1093/emboj/cdf637

Experimental method

X-RAY DIFFRACTION (3.1 Å)