5UIV

Structure of Thymidylate Kinase from Candida albicans Reveals Origin of Broad Substrate Specificity and a Novel Structural Element.

Summary for 5UIV

• Entry DOI: 10.2210/pdb5uiv/pdb
• Descriptor: Bifunctional thymidylate/uridylate kinase, THYMIDINE-5'-PHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: thymidylate kinase, candida albicans, transferase
• Biological source: Candida albicans SC5314 (Yeast)
• Total number of polymer chains: 1
• Total formula weight: 26688.31

Authors

Sinha, K.,Rule, G.S. (deposition date: 2017-01-15, release date: 2017-08-09, Last modification date: 2023-10-04)

Primary citation

Sinha, K.,Rule, G.S.
The Structure of Thymidylate Kinase from Candida albicans Reveals a Unique Structural Element.
Biochemistry, 56:4360-4370, 2017

PubMed Abstract: The structure of thymidylate kinase from Candida albicans, determined by X-ray crystallography, is reported to a resolution of 2.45 Å with a final R of 0.223. Thymidylate kinase from C. albicans possesses a unique 15-residue loop that is not seen in thymidylate kinases from other genera. The structure reported here reveals that the conformation of this loop is constrained by both intra- and intersubunit hydrogen bonding, and a number of key residues in this loop are conserved among different Candida species that are medically important. The substrate specificity of the enzyme was determined using a novel nuclear magnetic resonance-based assay as well as a traditional coupled assay. The enzyme is active against 3'-azido-3'-deoxythymidine monophosphate and moderately active with dGMP. The distinct functional and structural differences between the C. albicans enzyme and the human enzyme suggest that thymidylate kinase is an appropriate target for the development of new antifungal agents.

PubMed: 28742342
DOI: 10.1021/acs.biochem.7b00498

Experimental method

X-RAY DIFFRACTION (2.45 Å)