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PDBsum entry 1o2b
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1o2b

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
213 a.a. *
Ligands
PO4 ×3
FAD ×4
Waters ×240
* Residue conservation analysis
PDB id:
1o2b
Name: Transferase
Title: Crystal structure of thymidylate synthase complementing protein (tm0449) from thermotoga maritima with fad and po4 at 2.45 a resolution
Structure: Thymidylate synthase thyx. Chain: a, b, c, d. Synonym: ts, tsase, thymidylate synthase complementing protein. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Gene: tm0449. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.45Å     R-factor:   0.203     R-free:   0.265
Authors: I.I.Mathews,A.M.Deacon,J.M.Canaves,D.Mcmullan,S.A.Lesley,S.Agarwalla, P.Kuhn,Joint Center For Structural Genomics (Jcsg)
Key ref:
I.I.Mathews et al. (2003). Functional analysis of substrate and cofactor complex structures of a thymidylate synthase-complementing protein. Structure, 11, 677-690. PubMed id: 12791256 DOI: 10.1016/S0969-2126(03)00097-2
Date:
18-Feb-03     Release date:   24-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9WYT0  (THYX_THEMA) -  Flavin-dependent thymidylate synthase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)
Seq:
Struc: 		220 a.a.
213 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.148  - thymidylate synthase (FAD).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADPH + H+ = dTMP + (6S)-5,6,7,8-tetrahydrofolate + NADP+
dUMP
 + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate
 + NADPH
 + H(+)
Bound ligand (Het Group name = FAD)
matches with 71.19% similarity 		= dTMP
 + (6S)-5,6,7,8-tetrahydrofolate
 + NADP(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(03)00097-2 Structure 11:677-690 (2003)
PubMed id: 12791256  
 
 
Functional analysis of substrate and cofactor complex structures of a thymidylate synthase-complementing protein.
I.I.Mathews, A.M.Deacon, J.M.Canaves, D.McMullan, S.A.Lesley, S.Agarwalla, P.Kuhn.
 
  ABSTRACT  
 
Like thymidylate synthase (TS) in eukaryotes, the thymidylate synthase-complementing proteins (TSCPs) are mandatory for cell survival of many prokaryotes in the absence of external sources of thymidylate. Details of the mechanism of this novel family of enzymes are unknown. Here, we report the structural and functional analysis of a TSCP from Thermotoga maritima and its complexes with substrate, analogs, and cofactor. The structures presented here provide a basis for rationalizing the TSCP catalysis and reveal the possibility of the design of an inhibitor. We have identified a new helix-loop-strand FAD binding motif characteristic of the enzymes in the TSCP family. The presence of a hydrophobic core with residues conserved among the TSCP family suggests a common overall fold.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of TM0449(A) View of the monomer.(B) Topology diagram of the monomer (Westhead et al., 1998). b strands, filled black triangles; a helices, filled blue circles. Strand directions are indicated using upward-pointing or downward-pointing triangles. N and C termini are labeled.(C) View of the monomer orthogonal to the view in (A).(D) View of the tetramer showing bound FAD molecules. Flavin ring exposed to the surface in one of the monomers is shown with an arrow.(E) Orthogonal view of the tetramer. The paired FAD molecules on each side of the tetramer, cyan and black.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 677-690) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20716366 D.Weekes, S.S.Krishna, C.Bakolitsa, I.A.Wilson, A.Godzik, and J.Wooley (2010).
TOPSAN: a collaborative annotation environment for structural genomics.
  BMC Bioinformatics, 11, 426.  
19643076 E.M.Koehn, and A.Kohen (2010).
Flavin-dependent thymidylate synthase: a novel pathway towards thymine.
  Arch Biochem Biophys, 493, 96.  
19370033 E.M.Koehn, T.Fleischmann, J.A.Conrad, B.A.Palfey, S.A.Lesley, I.I.Mathews, and A.Kohen (2009).
An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene.
  Nature, 458, 919-923.
PDB codes: 3g4a 3g4c
19459936 Z.Wang, A.Chernyshev, E.M.Koehn, T.D.Manuel, S.A.Lesley, and A.Kohen (2009).
Oxidase activity of a flavin-dependent thymidylate synthase.
  FEBS J, 276, 2801-2810.  
18192395 J.E.Ulmer, Y.Boum, C.D.Thouvenel, H.Myllykallio, and C.H.Sibley (2008).
Functional analysis of the Mycobacterium tuberculosis FAD-dependent thymidylate synthase, ThyX, reveals new amino acid residues contributing to an extended ThyX motif.
  J Bacteriol, 190, 2056-2064.  
18270995 S.Ferrari, V.Losasso, and M.P.Costi (2008).
Sequence-based identification of specific drug target regions in the thymidylate synthase enzyme family.
  ChemMedChem, 3, 392-401.  
18648921 Y.Wang, and X.Zhang (2008).
Identification and characterization of a novel thymidylate synthase from deep-sea thermophilic bacteriophage Geobacillus virus E2.
  Virus Genes, 37, 218-224.  
17216455 A.Chernyshev, T.Fleischmann, and A.Kohen (2007).
Thymidyl biosynthesis enzymes as antibiotic targets.
  Appl Microbiol Biotechnol, 74, 282-289.  
17609801 A.Chernyshev, T.Fleischmann, E.M.Koehn, S.A.Lesley, and A.Kohen (2007).
The relationships between oxidase and synthase activities of flavin dependent thymidylate synthase (FDTS).
  Chem Commun (Camb), (), 2861-2863.  
16650981 A.Andreeva, and A.G.Murzin (2006).
Evolution of protein fold in the presence of functional constraints.
  Curr Opin Struct Biol, 16, 399-408.  
16609803 A.Mason, N.Agrawal, M.T.Washington, S.A.Lesley, and A.Kohen (2006).
A lag-phase in the reduction of flavin dependent thymidylate synthase (FDTS) revealed a mechanistic missing link.
  Chem Commun (Camb), (), 1781-1783.  
16857670 M.Graille, J.P.Baltaze, N.Leulliot, D.Liger, S.Quevillon-Cheruel, and H.van Tilbeurgh (2006).
Structure-based functional annotation: yeast ymr099c codes for a D-hexose-6-phosphate mutarotase.
  J Biol Chem, 281, 30175-30185.
PDB codes: 2ciq 2cir 2cis
16615077 R.R.Sotelo-Mundo, L.Changchien, F.Maley, and W.R.Montfort (2006).
Crystal structures of thymidylate synthase mutant R166Q: structural basis for the nearly complete loss of catalytic activity.
  J Biochem Mol Toxicol, 20, 88-92.
PDB codes: 1ffl 1fwm
15591067 J.Griffin, C.Roshick, E.Iliffe-Lee, and G.McClarty (2005).
Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase.
  J Biol Chem, 280, 5456-5467.  
15557262 G.Spraggon, D.Pantazatos, H.E.Klock, I.A.Wilson, V.L.Woods, and S.A.Lesley (2004).
On the use of DXMS to produce more crystallizable proteins: structures of the T. maritima proteins TM0160 and TM1171.
  Protein Sci, 13, 3187-3199.
PDB codes: 1o5l 1sj5 1vjl
15471872 S.Graziani, Y.Xia, J.R.Gurnon, J.L.Van Etten, D.Leduc, S.Skouloubris, H.Myllykallio, and U.Liebl (2004).
Functional analysis of FAD-dependent thymidylate synthase ThyX from Paramecium bursaria Chlorella virus-1.
  J Biol Chem, 279, 54340-54347.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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