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2vet

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Revision as of 21:13, 19 September 2018

CRYSTAL STRUCTURE OF THE THYMIDYLATE SYNTHASE K48Q COMPLEXED WITH DUMP

Structural highlights

2vet is a 1 chain structure with sequence from Ecobb. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1jg0, 1bid, 1jtu, 1ddu, 1bjg, 1axw, 2ftq, 1syn, 1tsd, 1ffl, 1bq1, 2kce, 1evf, 2ftn, 1dna, 1kce, 1jtq, 1f4g, 1f4f, 1tjs, 1fwm, 1an5, 1f4c, 1kzj, 1trg, 2bbq, 2g8o, 1tys, 1nce, 1jut, 1tlc, 2g8x, 1evg, 1qqq, 1ev8, 1tls, 1f4b, 1zpr, 2fto, 1kzi, 1f4e, 1bdu, 3tms, 2a9w, 1tdu, 2g8m, 1aob, 1bq2, 1aiq, 1f4d, 1ev5, 1ajm, 2tsc, 1tsn, 2vf0, 3b5b
Activity:	Thymidylate synthase, with EC number 2.1.1.45
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TYSY_ECOLI] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) using methylene tetrahydrofolate (CH(2)THF) as cofactor, the glutamate tail of which forms a water-mediated hydrogen bond with an invariant lysine residue of this enzyme. To understand the role of this interaction, we studied the K48Q mutant of Escherichia coli TS using structural and biophysical methods. The k(cat) of the K48Q mutant was 430-fold lower than wild-type TS in activity, while the K(m) for the (R)-stereoisomer of CH(2)THF was 300 microM, about 30-fold larger than K(m) from the wild-type TS. Affinity constants were determined using isothermal titration calorimetry, which showed that binding was reduced by one order of magnitude for folate-like TS inhibitors, such as propargyl-dideazafolate (PDDF) or compounds that distort the TS active site like BW1843U89 (U89). The crystal structure of the K48Q-dUMP complex revealed that dUMP binding is not impaired in the mutant, and that U89 in a ternary complex of K48Q-nucleotide-U89 was bound in the active site with subtle differences relative to comparable wild-type complexes. PDDF failed to form ternary complexes with K48Q and dUMP. Thermodynamic data correlated with the structural determinations, since PDDF binding was dominated by enthalpic effects while U89 had an important entropic component. In conclusion, K48 is critical for catalysis since it leads to a productive CH(2)THF binding, while mutation at this residue does not affect much the binding of inhibitors that do not make contact with this group.

Role of an invariant lysine residue in folate binding on Escherichia coli thymidylate synthase: calorimetric and crystallographic analysis of the K48Q mutant.,Arvizu-Flores AA, Sugich-Miranda R, Arreola R, Garcia-Orozco KD, Velazquez-Contreras EF, Montfort WR, Maley F, Sotelo-Mundo RR Int J Biochem Cell Biol. 2008;40(10):2206-17. Epub 2008 Mar 6. PMID:18403248^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Arvizu-Flores AA, Sugich-Miranda R, Arreola R, Garcia-Orozco KD, Velazquez-Contreras EF, Montfort WR, Maley F, Sotelo-Mundo RR. Role of an invariant lysine residue in folate binding on Escherichia coli thymidylate synthase: calorimetric and crystallographic analysis of the K48Q mutant. Int J Biochem Cell Biol. 2008;40(10):2206-17. Epub 2008 Mar 6. PMID:18403248 doi:10.1016/j.biocel.2008.02.025

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vet"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF THE THYMIDYLATE SYNTHASE K48Q COMPLEXED WITH DUMP==
 <StructureSection load='2vet' size='340' side='right' caption='[[2vet]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jg0|1jg0]], [[1bid|1bid]], [[1jtu|1jtu]], [[1ddu|1ddu]], [[1bjg|1bjg]], [[1axw|1axw]], [[2ftq|2ftq]], [[1syn|1syn]], [[1tsd|1tsd]], [[1ffl|1ffl]], [[1bq1|1bq1]], [[2kce|2kce]], [[1evf|1evf]], [[2ftn|2ftn]], [[1dna|1dna]], [[1kce|1kce]], [[1jtq|1jtq]], [[1f4g|1f4g]], [[1f4f|1f4f]], [[1tjs|1tjs]], [[1fwm|1fwm]], [[1an5|1an5]], [[1f4c|1f4c]], [[1kzj|1kzj]], [[1trg|1trg]], [[2bbq|2bbq]], [[2g8o|2g8o]], [[1tys|1tys]], [[1nce|1nce]], [[1jut|1jut]], [[1tlc|1tlc]], [[2g8x|2g8x]], [[1evg|1evg]], [[1qqq|1qqq]], [[1ev8|1ev8]], [[1tls|1tls]], [[1f4b|1f4b]], [[1zpr|1zpr]], [[2fto|2fto]], [[1kzi|1kzi]], [[1f4e|1f4e]], [[1bdu|1bdu]], [[3tms|3tms]], [[2a9w|2a9w]], [[1tdu|1tdu]], [[2g8m|2g8m]], [[1aob|1aob]], [[1bq2|1bq2]], [[1aiq|1aiq]], [[1f4d|1f4d]], [[1ev5|1ev5]], [[1ajm|1ajm]], [[2tsc|2tsc]], [[1tsn|1tsn]], [[2vf0|2vf0]], [[3b5b|3b5b]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vet OCA], [http://pdbe.org/2vet PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vet RCSB], [http://www.ebi.ac.uk/pdbsum/2vet PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vet OCA], [http://pdbe.org/2vet PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vet RCSB], [http://www.ebi.ac.uk/pdbsum/2vet PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vet ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2vet_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2vet_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 42: / Line 43: @@
 [[Category: Montfort, W R]]
 [[Category: Sotelo-Mundo, R R]]
+[[Category: Cytoplasm]]
 [[Category: Dump substrate]]
 [[Category: Methyltransferase]]

2vet

From Proteopedia

Revision as of 21:13, 19 September 2018

CRYSTAL STRUCTURE OF THE THYMIDYLATE SYNTHASE K48Q COMPLEXED WITH DUMP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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