Structural highlights
Function
[A0A0S4TER9_CRYHO] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389]
Publication Abstract from PubMed
Thymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R-enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and enzyme stereospecificity. To establish how C. hominis and human TS (ChTS and hTS) selectively discriminate 1 and 2, respectively, we determined crystal structures of ChTS complexed with 2 and hTS complexed with 1 or 2. Coupled with the previously determined structure of ChTS complexed with 1, we discuss a possible mechanism for enzyme stereospecificity and inhibitor selectivity. This article is protected by copyright. All rights reserved.
Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase.,Czyzyk DJ, Valhondo M, Jorgensen WL, Anderson KS FEBS Lett. 2019 Jun 7. doi: 10.1002/1873-3468.13474. PMID:31172516[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Czyzyk DJ, Valhondo M, Jorgensen WL, Anderson KS. Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase. FEBS Lett. 2019 Jun 7. doi: 10.1002/1873-3468.13474. PMID:31172516 doi:http://dx.doi.org/10.1002/1873-3468.13474
