7D9K

DNA binding domain of human DNA Ligase IV - Wild type

Summary for 7D9K

• Entry DOI: 10.2210/pdb7d9k/pdb
• Related: 4HTO
• Descriptor: DNA ligase 4 (2 entities in total)
• Functional Keywords: dbd, native, atp dependant ligase., ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27627.94

Authors

Maddi, E.R.,Raghavan, S.C.,Natesh, R. (deposition date: 2020-10-13, release date: 2021-02-24, Last modification date: 2023-11-29)

Primary citation

Maddi, E.R.,Raghavan, S.C.,Natesh, R.
Hypomorphic mutations in human DNA ligase IV lead to compromised DNA binding efficiency, hydrophobicity and thermal stability.
Protein Eng.Des.Sel., 34:-, 2021

PubMed Abstract: Studies have shown that Lig4 syndrome mutations in DNA ligase IV (LigIV) are compromised in its function with residual level of double strand break ligation activity in vivo. It was speculated that Lig4 syndrome mutations adversely affect protein folding and stability. Though there are crystal structures of LigIV, there are no reports of crystal structures of Lig4 syndrome mutants and their biophysical characterization to date. Here, we have examined the conformational states, thermal stability, hydrophobicity and DNA binding efficiency of human DNA LigIV wild type and its hypomorphic mutants by far-UV circular dichroism, tyrosine and tryptophan fluorescence, and 1-anilino-8-naphthalene-sulfonate binding, dynamic light scattering, size exclusion chromatography, multi-angle light scattering and electrophoretic mobility shift assay. We show here that LigIV hypomorphic mutants have reduced DNA-binding efficiency, a shift in secondary structure content from the helical to random coil, marginal reduction in their thermal stability and increased hydrophobicity as compared to the wild-type LigIV.

PubMed: 33586762
DOI: 10.1093/protein/gzab001

Experimental method

X-RAY DIFFRACTION (2.9 Å)