5DQO

Crystal structure of Y347F mutant of human primase p58 iron-sulfur cluster domain

Summary for 5DQO

• Entry DOI: 10.2210/pdb5dqo/pdb
• Related: 3L9Q
• Descriptor: DNA primase large subunit, IRON/SULFUR CLUSTER (3 entities in total)
• Functional Keywords: iron-sulfur cluster, dna priming, replication
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 92030.36

Authors

Salay, L.E.,Thompson, M.K.,Chazin, W.J. (deposition date: 2015-09-15, release date: 2016-09-21, Last modification date: 2023-09-27)

Primary citation

O'Brien, E.,Holt, M.E.,Thompson, M.K.,Salay, L.E.,Ehlinger, A.C.,Chazin, W.J.,Barton, J.K.
The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.
Science, 355:-, 2017

PubMed Abstract: DNA charge transport chemistry offers a means of long-range, rapid redox signaling. We demonstrate that the [4Fe4S] cluster in human DNA primase can make use of this chemistry to coordinate the first steps of DNA synthesis. Using DNA electrochemistry, we found that a change in oxidation state of the [4Fe4S] cluster acts as a switch for DNA binding. Single-atom mutations that inhibit this charge transfer hinder primase initiation without affecting primase structure or polymerization. Generating a single base mismatch in the growing primer duplex, which attenuates DNA charge transport, inhibits primer truncation. Thus, redox signaling by [4Fe4S] clusters using DNA charge transport regulates primase binding to DNA and illustrates chemistry that may efficiently drive substrate handoff between polymerases during DNA replication.

PubMed: 28232525
DOI: 10.1126/science.aag1789

Experimental method

X-RAY DIFFRACTION (2.3 Å)