spacer
spacer
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Isomerase PDB id
1eq2
Jmol
Contents
Protein chains
273 a.a. *
(+ 2 more) 300 a.a. *
Ligands
NAP ×10
ADQ ×10
Waters ×1056
* Residue conservation analysis
PDB id:
1eq2
Name: Isomerase
Title: The crystal structure of adp-l-glycero-d-mannoheptose 6- epimerase
Structure: Adp-l-glycero-d-mannoheptose 6-epimerase. Chain: a, b, c, d, e, f, g, h, i, j. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Pentamer (from PQS)
Resolution:
2.00Å     R-factor:   0.212     R-free:   0.262
Authors: A.M.Deacon,Y.S.Ni,W.G.Coleman Jr.,S.E.Ealick
Key ref:
A.M.Deacon et al. (2000). The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. Structure, 8, 453-462. PubMed id: 10896473 DOI: 10.1016/S0969-2126(00)00128-3
Date:
31-Mar-00     Release date:   08-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P67910  (HLDD_ECOLI) -  ADP-L-glycero-D-manno-heptose-6-epimerase
Seq:
Struc: 		310 a.a.
273 a.a.*
Protein chains
Pfam   ArchSchema ?
P67910  (HLDD_ECOLI) -  ADP-L-glycero-D-manno-heptose-6-epimerase
Seq:
Struc: 		310 a.a.
300 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H, I, J: E.C.5.1.3.20  - ADP-glyceromanno-heptose 6-epimerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ADP-D-glycero-D-manno-heptose = ADP-L-glycero-D-manno-heptose
ADP-D-glycero-D-manno-heptose
Bound ligand (Het Group name = ADQ)
matches with 95.00% similarity 		= ADP-L-glycero-D-manno-heptose
      Cofactor: NAD(+)
NAD(+)
Bound ligand (Het Group name = NAP) matches with 91.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     response to stress   4 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(00)00128-3 Structure 8:453-462 (2000)
PubMed id: 10896473  
 
 
The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist.
A.M.Deacon, Y.S.Ni, W.G.Coleman, S.E.Ealick.
 
  ABSTRACT  
 
BACKGROUND: ADP-L-glycero--mannoheptose 6-epimerase (AGME) is required for lipopolysaccharide (LPS) biosynthesis in most genera of pathogenic and non-pathogenic Gram-negative bacteria. It catalyzes the interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, a precursor of the seven-carbon sugar L-glycero-mannoheptose (heptose). Heptose is an obligatory component of the LPS core domain; its absence results in a truncated LPS structure resulting in susceptibility to hydrophobic antibiotics. Heptose is not found in mammalian cells, thus its biosynthetic pathway in bacteria presents a unique target for the design of novel antimicrobial agents. RESULTS: The structure of AGME, in complex with NADP and the catalytic inhibitor ADP-glucose, has been determined at 2.0 A resolution by multiwavelength anomalous diffraction (MAD) phasing methods. AGME is a homopentameric enzyme, which crystallizes with two pentamers in the asymmetric unit. The location of 70 crystallographically independent selenium sites was a key step in the structure determination process. Each monomer comprises two domains: a large N-terminal domain, consisting of a modified seven-stranded Rossmann fold that is associated with NADP binding; and a smaller alpha/beta C-terminal domain involved in substrate binding. CONCLUSIONS: The first structure of an LPS core biosynthetic enzyme leads to an understanding of the mechanism of the conversion between ADP-D-glycero--mannoheptose and ADP-L-glycero-D-mannoheptose. On the basis of its high structural similarity to UDP-galactose epimerase and the three-dimensional positions of the conserved residues Ser116, Tyr140 and Lys144, AGME was classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily. This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Structure of the AGME pentamer. (a) Ribbon representation of the AGME pentamer with space-filling representations of NADP and ADP-glucose. (b) Corey, Pauling and Koltun (CPK) space-filling representation of the AGME pentamer (N-terminal domain in green; C-terminal domain in blue). (c,d) van der Waals surface representation of AGME. The surface is colored according to electrostatic potential: blue for positive and red for negative. The bottom surface (d) is very negative. The top view (c) is less interesting electrostatically, but does show the overall shape with the small substrate-binding domain arranged on top of the larger NADP-binding domain. The figure was prepared using the program GRASP [34].
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 453-462) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
20506248 T.Kowatz, J.P.Morrison, M.E.Tanner, and J.H.Naismith (2010).
The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism.
  Protein Sci, 19, 1337-1343.
PDB codes: 2x6t 2x86
19663400 X.Liu, and C.T.Walsh (2009).
Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan.
  Biochemistry, 48, 8746-8757.  
19058030 Y.Kim, H.Li, T.A.Binkowski, D.Holzle, and A.Joachimiak (2009).
Crystal structure of fatty acid/phospholipid synthesis protein PlsX from Enterococcus faecalis.
  J Struct Funct Genomics, 10, 157-163.
PDB code: 1u7n
18227433 F.R.Salsbury, S.T.Knutson, L.B.Poole, and J.S.Fetrow (2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
  Protein Sci, 17, 299-312.  
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
18625333 M.E.Tanner (2008).
Transient oxidation as a mechanistic strategy in enzymatic catalysis.
  Curr Opin Chem Biol, 12, 532-538.  
16531240 A.H.Ehrensberger, R.A.Elling, and D.K.Wilson (2006).
Structure-guided engineering of xylitol dehydrogenase cosubstrate specificity.
  Structure, 14, 567-575.
PDB code: 1zem
16936924 J.H.Naismith (2006).
Inferring the chemical mechanism from structures of enzymes.
  Chem Soc Rev, 35, 763-770.  
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
15583400 C.Ma, and G.Chang (2004).
Crystallography of the integral membrane protein EmrE from Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 60, 2399-2402.  
14739333 N.A.Webb, A.M.Mulichak, J.S.Lam, H.L.Rocchetta, and R.M.Garavito (2004).
Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
  Protein Sci, 13, 529-539.
PDB code: 1rpn
12642575 N.M.Koropatkin, H.W.Liu, and H.M.Holden (2003).
High resolution x-ray structure of tyvelose epimerase from Salmonella typhi.
  J Biol Chem, 278, 20874-20881.
PDB code: 1orr
12004063 C.Creuzenet, R.V.Urbanic, and J.S.Lam (2002).
Structure-function studies of two novel UDP-GlcNAc C6 dehydratases/C4 reductases. Variation from the SYK dogma.
  J Biol Chem, 277, 26769-26778.  
12045108 C.R.Raetz, and C.Whitfield (2002).
Lipopolysaccharide endotoxins.
  Annu Rev Biochem, 71, 635-700.  
11752776 E.Micossi, W.N.Hunter, and G.A.Leonard (2002).
De novo phasing of two crystal forms of tryparedoxin II using the anomalous scattering from S atoms: a combination of small signal and medium resolution reveals this to be a general tool for solving protein crystal structures.
  Acta Crystallogr D Biol Crystallogr, 58, 21-28.
PDB codes: 1o6j 1o81
12230552 Y.Kallberg, U.Oppermann, H.Jörnvall, and B.Persson (2002).
Short-chain dehydrogenases/reductases (SDRs).
  Eur J Biochem, 269, 4409-4417.  
  11470438 A.A.McCarthy, H.M.Baker, S.C.Shewry, M.L.Patchett, and E.N.Baker (2001).
Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold.
  Structure, 9, 637-646.
PDB codes: 1jc4 1jc5
11006535 S.E.Ealick (2000).
Advances in multiple wavelength anomalous diffraction crystallography.
  Curr Opin Chem Biol, 4, 495-499.  
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.