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PDBsum entry 1epz

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Isomerase PDB id
1epz
Jmol
Contents
Protein chain
183 a.a. *
Ligands
TYD
Waters ×119
* Residue conservation analysis
PDB id:
1epz
Name: Isomerase
Title: Crystal structure of dtdp-6-deoxy-d-xylo-4-hexuloase 3,5-epi from methanobacterium thermoautotrophicum with bound ligand
Structure: Dtdp-6-deoxy-d-xylo-4-hexulose 3,5-epimerase. Chain: a. Synonym: dtdp-4-dehydrorhamnose 3,5-epimerase. Engineered: yes
Source: Methanothermobacter thermautotrophicus organism_taxid: 145262. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
1.75Å     R-factor:   0.196     R-free:   0.225
Authors: D.Christendat,V.Saridakis,A.Bochkarev,E.F.Pai,C.Arrowsmith, A.M.Edwards
Key ref:
D.Christendat et al. (2000). Crystal structure of dTDP-4-keto-6-deoxy-D-hexulose 3,5-epimerase from Methanobacterium thermoautotrophicum complexed with dTDP. J Biol Chem, 275, 24608-24612. PubMed id: 10827167 DOI: 10.1074/jbc.C000238200
Date:
30-Mar-00     Release date:   13-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O27818  (RMLC_METTH) -  dTDP-4-dehydrorhamnose 3,5-epimerase
Seq:
Struc:
185 a.a.
183 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.1.3.13  - dTDP-4-dehydrorhamnose 3,5-epimerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
6-Deoxyhexose Biosynthesis
      Reaction: dTDP-4-dehydro-6-deoxy-alpha-D-glucose = dTDP-4-dehydro-beta-L-rhamnose
dTDP-4-dehydro-6-deoxy-alpha-D-glucose
Bound ligand (Het Group name = TYD)
matches with 71.43% similarity
= dTDP-4-dehydro-beta-L-rhamnose
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     lipopolysaccharide biosynthetic process   3 terms 
  Biochemical function     isomerase activity     2 terms  

 

 
    Key reference    
 
 
DOI no: 10.1074/jbc.C000238200 J Biol Chem 275:24608-24612 (2000)
PubMed id: 10827167  
 
 
Crystal structure of dTDP-4-keto-6-deoxy-D-hexulose 3,5-epimerase from Methanobacterium thermoautotrophicum complexed with dTDP.
D.Christendat, V.Saridakis, A.Dharamsi, A.Bochkarev, E.F.Pai, C.H.Arrowsmith, A.M.Edwards.
 
  ABSTRACT  
 
Deoxythymidine diphosphate (dTDP)-4-keto-6-deoxy-d-hexulose 3, 5-epimerase (RmlC) is involved in the biosynthesis of dTDP-l-rhamnose, which is an essential component of the bacterial cell wall. The crystal structure of RmlC from Methanobacterium thermoautotrophicum was determined in the presence and absence of dTDP, a substrate analogue. RmlC is a homodimer comprising a central jelly roll motif, which extends in two directions into longer beta-sheets. Binding of dTDP is stabilized by ionic interactions to the phosphate group and by a combination of ionic and hydrophobic interactions with the base. The active site, which is located in the center of the jelly roll, is formed by residues that are conserved in all known RmlC sequence homologues. The conservation of the active site residues suggests that the mechanism of action is also conserved and that the RmlC structure may be useful in guiding the design of antibacterial drugs.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Overview of the dimeric structure of RmlC. Ribbon diagram of the RmlC dimer with a ball-and-stick model of complexed dTDP. Each subunit is colored differently. A, 2-fold axis of symmetry in the plane. B, rotation of A by 90° in the plane.
Figure 4.
Fig. 4. A detailed view of the active site of RmlC. A, residues involved in binding dTDP and the location of the His-64-Asp-172 catalytic dyad are shown. Residues are color-coded based on whether they originate from subunit A (yellow) or B (blue), and the catalytic triad is colored green. B, a schematic two-dimensional structure of the active site of RmlC is shown. Residues and water molecules interacting with complexed dTDP are shown.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 24608-24612) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19473032 E.W.Moomaw, A.Angerhofer, P.Moussatche, A.Ozarowski, I.García-Rubio, and N.G.Richards (2009).
Metal dependence of oxalate decarboxylase activity.
  Biochemistry, 48, 6116-6125.  
19478949 G.Agarwal, M.Rajavel, B.Gopal, and N.Srinivasan (2009).
Structure-based phylogeny as a diagnostic for functional characterization of proteins with a cupin fold.
  PLoS One, 4, e5736.  
  19058170 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
  Angew Chem Int Ed Engl, 47, 9814-9859.  
17691895 B.Y.Chen, V.Y.Fofanov, D.H.Bryant, B.D.Dodson, D.M.Kristensen, A.M.Lisewski, M.Kimmel, O.Lichtarge, and L.E.Kavraki (2007).
The MASH pipeline for protein function prediction and an algorithm for the geometric refinement of 3D motifs.
  J Comput Biol, 14, 791-816.  
17046787 C.Dong, L.L.Major, V.Srikannathasan, J.C.Errey, M.F.Giraud, J.S.Lam, M.Graninger, P.Messner, M.R.McNeil, R.A.Field, C.Whitfield, and J.H.Naismith (2007).
RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation.
  J Mol Biol, 365, 146-159.
PDB codes: 2ixc 2ixh 2ixi 2ixj 2ixk 2ixl
16855251 M.N.Hung, E.Rangarajan, C.Munger, G.Nadeau, T.Sulea, and A.Matte (2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
  J Bacteriol, 188, 5606-5617.
PDB codes: 2fs5 2ft0
16411240 P.Jakimowicz, M.Tello, C.L.Meyers, C.T.Walsh, M.J.Buttner, R.A.Field, and D.M.Lawson (2006).
The 1.6-A resolution crystal structure of NovW: a 4-keto-6-deoxy sugar epimerase from the novobiocin biosynthetic gene cluster of Streptomyces spheroides.
  Proteins, 63, 261-265.
PDB code: 2c0z
16077096 A.Teplyakov, G.Obmolova, J.Toedt, M.Y.Galperin, and G.L.Gilliland (2005).
Crystal structure of the bacterial YhcH protein indicates a role in sialic acid catabolism.
  J Bacteriol, 187, 5520-5527.
PDB code: 1s4c
15608122 C.Z.Zhou, P.Meyer, S.Quevillon-Cheruel, I.L.De La Sierra-Gallay, B.Collinet, M.Graille, K.Blondeau, J.M.François, N.Leulliot, I.Sorel, A.Poupon, J.Janin, and H.Van Tilbeurgh (2005).
Crystal structure of the YML079w protein from Saccharomyces cerevisiae reveals a new sequence family of the jelly-roll fold.
  Protein Sci, 14, 209-215.
PDB codes: 1xe7 1xe8
15735308 S.Singh, S.Korolev, O.Koroleva, T.Zarembinski, F.Collart, A.Joachimiak, and D.Christendat (2005).
Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae.
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PDB code: 1npy
15716432 T.Hansen, B.Schlichting, M.Felgendreher, and P.Schönheit (2005).
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  J Bacteriol, 187, 1621-1631.  
14705034 C.M.Viola, V.Saridakis, and D.Christendat (2004).
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  Proteins, 54, 166-169.
PDB code: 1q1l
15103135 K.A.Kantardjieff, C.Y.Kim, C.Naranjo, G.S.Waldo, T.Lekin, B.W.Segelke, A.Zemla, M.S.Park, T.C.Terwilliger, and B.Rupp (2004).
Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway.
  Acta Crystallogr D Biol Crystallogr, 60, 895-902.
PDB code: 1upi
15704011 R.Sanishvili, M.Pennycooke, J.Gu, X.Xu, A.Joachimiak, A.M.Edwards, and D.Christendat (2004).
Crystal structure of the hypothetical protein TA1238 from Thermoplasma acidophilum: a new type of helical super-bundle.
  J Struct Funct Genomics, 5, 231-240.
PDB code: 1nig
14555659 Y.Kim, A.F.Yakunin, E.Kuznetsova, X.Xu, M.Pennycooke, J.Gu, F.Cheung, M.Proudfoot, C.H.Arrowsmith, A.Joachimiak, A.M.Edwards, and D.Christendat (2004).
Structure- and function-based characterization of a new phosphoglycolate phosphatase from Thermoplasma acidophilum.
  J Biol Chem, 279, 517-526.
PDB code: 1l6r
12557182 A.Savchenko, A.Yee, A.Khachatryan, T.Skarina, E.Evdokimova, M.Pavlova, A.Semesi, J.Northey, S.Beasley, N.Lan, R.Das, M.Gerstein, C.H.Arrowmith, and A.M.Edwards (2003).
Strategies for structural proteomics of prokaryotes: Quantifying the advantages of studying orthologous proteins and of using both NMR and X-ray crystallography approaches.
  Proteins, 50, 392-399.  
12876368 P.Jakimowicz, C.L.Freel Meyers, C.T.Walsh, M.J.Buttner, and D.M.Lawson (2003).
Crystallization and preliminary X-ray studies on the putative dTDP sugar epimerase NovW from the novobiocin biosynthetic cluster of Streptomyces spheroides.
  Acta Crystallogr D Biol Crystallogr, 59, 1507-1509.  
12021439 D.Christendat, V.Saridakis, Y.Kim, P.A.Kumar, X.Xu, A.Semesi, A.Joachimiak, C.H.Arrowsmith, and A.M.Edwards (2002).
The crystal structure of hypothetical protein MTH1491 from Methanobacterium thermoautotrophicum.
  Protein Sci, 11, 1409-1414.
PDB code: 1l1s
12402029 T.C.Pochapsky, S.S.Pochapsky, T.Ju, H.Mo, F.Al-Mjeni, and M.J.Maroney (2002).
Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae.
  Nat Struct Biol, 9, 966-972.
PDB code: 1m4o
12012346 V.Saridakis, D.Christendat, A.Thygesen, C.H.Arrowsmith, A.M.Edwards, and E.F.Pai (2002).
Crystal structure of Methanobacterium thermoautotrophicum conserved protein MTH1020 reveals an NTN-hydrolase fold.
  Proteins, 48, 141-143.
PDB code: 1kuu
11738598 J.M.Dunwell, A.Culham, C.E.Carter, C.R.Sosa-Aguirre, and P.W.Goodenough (2001).
Evolution of functional diversity in the cupin superfamily.
  Trends Biochem Sci, 26, 740-746.  
11406387 S.A.Teichmann, A.G.Murzin, and C.Chothia (2001).
Determination of protein function, evolution and interactions by structural genomics.
  Curr Opin Struct Biol, 11, 354-363.  
11114506 M.F.Giraud, and J.H.Naismith (2000).
The rhamnose pathway.
  Curr Opin Struct Biol, 10, 687-696.  
11118200 W.Blankenfeldt, M.Asuncion, J.S.Lam, and J.H.Naismith (2000).
The structural basis of the catalytic mechanism and regulation of glucose-1-phosphate thymidylyltransferase (RmlA).
  EMBO J, 19, 6652-6663.
PDB codes: 1fxo 1fzw 1g0r 1g1l 1g23 1g2v 1g3l
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.