4WRU

Crystal structure of Mycobacterium tuberculosis uracil-DNA glycosylase in complex with uracil, Form II

Summary for 4WRU

• Entry DOI: 10.2210/pdb4wru/pdb
• Related: 4WRV 4WRW 4WRX 4WRY 4WRZ 4WS0 4WS1 4WS2 4WS3 4WS4 4WS5 4WS6 4WS7 4WS8
• Descriptor: Uracil-DNA glycosylase, URACIL, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: dna-repair, excision repair, conformational selection, ligand-binding, hydrolase
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm : P9WFQ9
• Total number of polymer chains: 1
• Total formula weight: 26053.18

Authors

Arif, S.M.,Geethanandan, K.,Mishra, P.,Surolia, A.,Varshney, U.,Vijayan, M. (deposition date: 2014-10-25, release date: 2015-07-15, Last modification date: 2023-09-27)

Primary citation

Arif, S.M.,Geethanandan, K.,Mishra, P.,Surolia, A.,Varshney, U.,Vijayan, M.
Structural plasticity in Mycobacterium tuberculosis uracil-DNA glycosylase (MtUng) and its functional implications.
Acta Crystallogr.,Sect.D, 71:1514-1527, 2015

PubMed Abstract: 17 independent crystal structures of family I uracil-DNA glycosylase from Mycobacterium tuberculosis (MtUng) and its complexes with uracil and its derivatives, distributed among five distinct crystal forms, have been determined. Thermodynamic parameters of binding in the complexes have been measured using isothermal titration calorimetry. The two-domain protein exhibits open and closed conformations, suggesting that the closure of the domain on DNA binding involves conformational selection. Segmental mobility in the enzyme molecule is confined to a 32-residue stretch which plays a major role in DNA binding. Uracil and its derivatives can bind to the protein in two possible orientations. Only one of them is possible when there is a bulky substituent at the 5' position. The crystal structures of the complexes provide a reasonable rationale for the observed thermodynamic parameters. In addition to providing fresh insights into the structure, plasticity and interactions of the protein molecule, the results of the present investigation provide a platform for structure-based inhibitor design.

PubMed: 26143923
DOI: 10.1107/S1399004715009311

Experimental method

X-RAY DIFFRACTION (1.24 Å)