Structural highlights
7sr6 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.62Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
POK11_HUMAN Early post-infection, the reverse transcriptase converts the viral RNA genome into double-stranded viral DNA. The RNase H domain of the reverse transcriptase performs two functions. It degrades the RNA template and specifically removes the RNA primer from the RNA/DNA hybrid. Following nuclear import, the integrase catalyzes the insertion of the linear, double-stranded viral DNA into the host cell chromosome. Endogenous Pol proteins may have kept, lost or modified their original function during evolution (By similarity).
Publication Abstract from PubMed
Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome and are derived from ancient integrations of retroviruses into the germline. The biology of HERVs is poorly defined, but there is accumulating evidence supporting pathological roles in diverse diseases, such as cancer, autoimmune, and neurodegenerative diseases. Functional proteins are produced by HERV-encoded genes, including reverse transcriptases (RTs), which could be a contributor to the pathology attributed to aberrant HERV-K expression. To facilitate the discovery and development of HERV-K RT potent and selective inhibitors, we expressed active HERV-K RT and determined the crystal structure of a ternary complex of this enzyme with a double-stranded DNA substrate. We demonstrate a range of RT inhibition with antiretroviral nucleotide analogs, while classic nonnucleoside analogs do not inhibit HERV-K RT. Detailed comparisons of HERV-K RT with other known RTs demonstrate similarities to diverse RT families and a striking similarity to the HIV-1 RT asymmetric heterodimer. Our analysis further reveals opportunities for selective HERV-K RT inhibition.
Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-K-specific inhibition.,Baldwin ET, Gotte M, Tchesnokov EP, Arnold E, Hagel M, Nichols C, Dossang P, Lamers M, Wan P, Steinbacher S, Romero DL Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2200260119. doi: , 10.1073/pnas.2200260119. Epub 2022 Jun 30. PMID:35771941[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baldwin ET, Götte M, Tchesnokov EP, Arnold E, Hagel M, Nichols C, Dossang P, Lamers M, Wan P, Steinbacher S, Romero DL. Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-K-specific inhibition. Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2200260119. PMID:35771941 doi:10.1073/pnas.2200260119
