4KAS

Crystal structure of FDTS from T. maritima mutant (H53D) with FAD and dUMP

Summary for 4KAS

• Entry DOI: 10.2210/pdb4kas/pdb
• Related: 4KAR 4KAT
• Descriptor: Thymidylate synthase ThyX, 2'-DEOXYURIDINE-5'-MONOPHOSPHATE, SULFATE ION, ... (8 entities in total)
• Functional Keywords: thyx, fdts, fad, dump, novel fdts fold, convertion of dump to dtmp using tetrahydrofolate, and nad(p)hc, transferase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 4
• Total formula weight: 113155.17

Authors

Mathews, I.I. (deposition date: 2013-04-22, release date: 2014-03-26, Last modification date: 2023-09-20)

Primary citation

Mathews, I.I.
Flavin-Dependent Thymidylate Synthase as a Drug Target for Deadly Microbes: Mutational Study and a Strategy for Inhibitor Design.
J Bioterror Biodef, Suppl 12:004-004, 2013

PubMed Abstract: The identification of flavin-dependent thymidylate synthase (FDTS) as an essential enzyme and its occurrence in several pathogenic microbes opens opportunities for using FDTS enzyme as an excellent target for new antimicrobial drug discovery. In contrast to the human thymidylate synthase enzyme that utilizes methylene-tetrahydrofolate (CHH folate) for the conversion of dUMP to dTMP, the microbial enzymes utilize an additional non-covalently bound FAD molecule for the hydride transfer from NAD(P)H. The structural and mechanistic differences between the human and microbial enzymes present an attractive opportunity for the design of antimicrobial compounds specific for the pathogens. We have determined the crystal structure of FDTS enzyme in complex with the methyl donor, CHH folate. We describe here the structure of a FDTS mutant and compare it with other FDTS complex structures, including a FDTS-CHH folate complex. We identified a conformational change essential for substrate binding and propose a strategy for the design of FDTS specific inhibitors.

PubMed: 24563811
DOI: 10.4172/2157-2526.S12-004

Experimental method

X-RAY DIFFRACTION (1.85 Å)