Crystal Structure of a Leukemia-Linked cN-II Mutant Bound to dATP and Phosphate

A structural mapping shows that 90% of leukemia-specific NT5C2 alleles affect two regulatory hotspots within the cytosolic purine 5'-nucleotidase molecule. The dataset, from a study by Aleš Hnizda at the University of Cambridge, describes the crystal structure of the D52N/R367Q cN-II mutant bound to dATP and free phosphate. It provides a structural basis for understanding how activating mutations in NT5C2 confer chemoresistance in relapsed acute lymphoblastic leukemia.

Use Cases

• Predicting drug resistance mutations in NT5C2 based on structural mapping of regulatory hotspots.
• Analyzing intersubunit activation transmission in hetero-oligomeric complexes combining wild-type and mutant subunits.
• Studying the structural basis of constitutive enzyme activity resulting from mutations that confer independence from allosteric ATP effects.

Strengths

• Structural mapping identifies that 90% of patient-derived leukemia alleles affect two specific regulatory hotspots.
• Analysis includes hetero-tetramer complexes, showing activation transmission from mutated to wild-type subunits.

Limitations

• Column-level documentation is absent; field semantics must be inferred after download.
• Row count is unknown, which may limit suitability assessment.
• Last update date is unknown; freshness unverified.

Provenance

Source

University of Cambridge

Collection Method

Likely derived from X-ray crystallography experiments described in the associated research paper.