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Thymidylate synthase

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{{STRUCTURE_4tmk| PDB=4tmk | SIZE=400| SCENE= |right|CAPTION=Human thymidylate synthase complex with UMP and the drug raltitrexed, [[4tmk]] }}
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{{STRUCTURE_4tmk| PDB=4tmk | SIZE=400| SCENE= |right|CAPTION=E. coli thymidylate synthase complex with bisubstrate inhibitor, [[4tmk]] }}
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Revision as of 10:59, 18 November 2012

Template:STRUCTURE 4tmk Thymidylate synthase (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair. TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. In protozoa, dihydrofolate reductase (DHFR) and TS are expressed as a bifunctional monomeric enzyme (DHFR-TS) with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases.

3D structures of thymidylate synthase

3tms, 1tjs, 1f4b, 2ftq – EcTS – Escherichia coli
1ajm, 1bq2, 1qqq, 1ev5, 1ev8, 1evf, 1evg, 1ffl, 2g8x, 2ftn - EcTS (mutant)
4tms, 1tda - LcTS – Lactobacillus casei
1tsw, 1tsz - LcTS (mutant)
1tis – TS – Enterobacteria phage T4
1bsf, 1bko, 1bkp, 1bsp - BsTS - Bacillus subtilis
1hw3, 1hw4, 1hzw, 1ypv, 2onb - hTS – human
3n5g – hTS His-tag
2rd8, 2rda, 3egy, 3ehi, 3eaw, 3ebu, 3ed7, 3edw, 3ef9, 3ejl, 3gg5, 3gh0, 3gh2 – hTS (mutant)
3ix6 – BmTS – Brucella melitensis
3kgb – TS – Encephalitozoon cuniculi
3ihi – mTS – mouse
3ge9 - CgTS – Corynebacterium glutamicum
3v8h – TS – Burkholderia thailandensis

Thymidylate synthase binary complex

1tdc, 1thy, 2tdm – LcTS + UMP
1tsv, 1tsx, 1tsy, 1njd, 1njb, 1vza, 1vzb, 1jmf, 1jmg, 1jmh, 1jmi, 1bo7, 1bo8, 1bp6, 1bpj, 1bp0, 2g86, 2g89, 2g8a, 2g8d - LcTS (mutant) + UMP
1vzc - LcTS (mutant) + fluoro-UMP
1nja, 1njc - LcTS (mutant) + CMP
1nje - LcTS + CMP
1tdb - LcTS + fluoro-UMP
1tsl, 1tsm - LcTS + inhibitor
4tmk, 5tmp - EcTS + inhibitor
1an5 - EcTS + inhibitor
1fwm - EcTS (mutant) + inhibitor
1bid - EcTS + UMP
1aob, 1bdu - EcTS + deoxyuridine derivative
1f4c, 1f4e - EcTS + tosyl-proline derivative
1f4d - EcTS (mutant) + tosyl-proline derivative
1f4f, 1f4g - EcTS + glutamyl-proline derivative
2vet - EcTS (mutant) + UMP
3b9h - EcTS + nitro-UMP
3bfi - EcTS (mutant) + nitro-UMP
1tmk - TS + TMP – yeast
3h9k - hTS (mutant) + fluoro-UMP
3hb8 - hTS (mutant) + UMP
3ob7 - hTS (mutant) + glutathione
3n5e - hTS + peptide inhibitor
4dq1 - TS + UMP – Staphylococcus aureus
4e5o - mTS + UMP

Thymidylate synthase ternary complex

2tdd - LcTS + inhibitor+ fluoro-UMP
1vzd - LcTS (mutant) + inhibitor+ fluoro-UMP
1vze, 1tvu, 1tvv, 1tvw - LcTS (mutant) + inhibitor+ UMP
1lca, 1lce, 3bnz - LcTS + inhibitor+ UMP
1lcb - LcTS + inhibitor+ TMP
3byx, 3bz0, 3c06, 3c0a, 3ijz, 3ik0, 3ik1 - LcTS + phthalimidic derivative + UMP
1tys - EcTS + inhibitor+ TMP
2fto, 3bgx - EcTS (mutant) + inhibitor+ TMP
1tlc - EcTS + inhibitor+ GMP
1syn, 1tsd - EcTS + inhibitor+ UMP
2bbq, 2tsc, 1kce, 1trg, 1kzi - EcTS + inhibitor+ UMP
1zpr, 1aiq, 1dna, 1bq1, 1kzj, 2vf0, 3b5b - EcTS (mutant) + inhibitor+ UMP
1tls, 1tsn - EcTS + inhibitor+ fluoro-UMP
3bhl, 3bhr - EcTS + inhibitor+ nitro-UMP
1bjg - EcTS (mutant) + inhibitor+ fluoro-UMP
2kce, 1axw - EcTS + drug + UMP
1jtq, 1jtu, 1jut, 1jg0, 2a9w, 2g8o - EcTS + inhibitor+ UMP
1nce, 2g8m - EcTS (mutant) + inhibitor+ UMP
1ddu, 1tdu - EcTS + deoxyuridine derivative + inhibitor
1rts, 2tsr - TS + drug + UMP – rat
1hvy, 1i00 - hTS + drug + UMP
1e2d, 1e2e, 1e2f - hTS (mutant) + ADP + TMP
1ju6, 1juj - hTS (mutant) + inhibitor+ UMP
1b02 - BsTS + inhibitor+ fluoro-UMP
1ci7 - PcTS + inhibitor+ UMP – Pneumocystis carinii
1f28 - PcTS + inhibitor+ UMP
2aaz - TS + inhibitor+ UMP – Filobasidiella neoformans
3qj7 - MtTS + spermine + UMP – Mycobacterium tuberculosis
4eb4 - mTS + drug + UMP

Bifunctional dihydrofolate reductase-thymidylate synthase

3i3r - DHFR-TS – Babesia bovis

DHFR-TS binary complex

3irm - TcDHFR-TS + inhibitor
3kjr - BmDHFR-TS + NADP

DHFR-TS ternary complex

2h2q - TcDHFR-TS + NADP + UMP – Trypanosoma cruzi
3clb, 3hbb - TcDHFR-TS + NADP + drug
3kjs, 3irn, 3iro, 3rg9 - TcDHFR-TS + NADP + inhibitor

DHFR-TS quaternary complex

1j3i, 3dga, 3qgt – PfDHFR-TS + NADP + inhibitor+ UMP – Plasmodium falciparum
1j3j, 1j3k, 3dg8, 3jsu, 3qg2 - PfDHFR-TS (mutant) + NADP + inhibitor+ UMP
1qzf, 1sej - ChDHFR-TS + NADP + inhibitor+ UMP – Cryprosporidium hominis
2oip - ChDHFR-TS (mutant) + NADP + inhibitor+ drug + UMP
3dl5, 3dl6 - ChDHFR-TS (mutant) + NADP + inhibitor+ dihydrofolic acid + UMP
3hj3 - ChDHFR-TS (mutant) + NADP + drug + UMP
3k2h - BmDHFR-TS + NADP + inhibitor+ UMP
3nrr - BmDHFR-TS + NADP + drug + UMP
3cl9 - TcDHFR-TS + NADP + drug + UMP
3inv - TcDHFR-TS + NADP + inhibitor+ UMP

Flavin-dependent thymidylate synthase

2af6 - MtTS + FAD + bromo-UMP
3hzg - MtTS + FAD
3gwc - MtTS + FAD + fluoro-UMP
2cfa - TS + FAD – Paramecium bursaria chlorella virus
2gq2 - MtTS (mutant) + NADP
3g4a, 3g4c, 3n0b, 3n0c - TS (mutant) + FAD + UMP – Thermotoga maritima
3fnn - CgTS + FAD
3ah5, 3n3y - TS + FAD + UMP – Helicobacter pylori

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