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PDBsum entry 2gej

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protein ligands links
Transferase PDB id
2gej
Jmol
Contents
Protein chain
361 a.a. *
Ligands
GDD
Waters ×23
* Residue conservation analysis
PDB id:
2gej
Name: Transferase
Title: Crystal structure of phosphatidylinositol mannosyltransferas from mycobacterium smegmatis in complex with gdp-man
Structure: Phosphatidylinositol mannosyltransferase (pima). Chain: a. Engineered: yes
Source: Mycobacterium smegmatis. Organism_taxid: 246196. Strain: mc2 155. Gene: pima. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.60Å     R-factor:   0.196     R-free:   0.245
Authors: M.E.Guerin,A.Buschiazzo,J.Kordulakova,M.Jackson,P.M.Alzari
Key ref: M.E.Guerin et al. (2007). Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria. J Biol Chem, 282, 20705-20714. PubMed id: 17510062
Date:
20-Mar-06     Release date:   03-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
A0QWG6  (PIMA_MYCS2) -  GDP-mannose-dependent alpha-(1-2)-phosphatidylinositol mannosyltransferase
Seq:
Struc:
386 a.a.
361 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.1.57  - Phosphatidylinositol alpha-mannosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Transfers one or more alpha-D-mannose units from GDP-mannose to positions 2,6- and others in 1-phosphatidyl-myo-inositol.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     biosynthetic process   7 terms 
  Biochemical function     transferase activity     4 terms  

 

 
J Biol Chem 282:20705-20714 (2007)
PubMed id: 17510062  
 
 
Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.
M.E.Guerin, J.Kordulakova, F.Schaeffer, Z.Svetlikova, A.Buschiazzo, D.Giganti, B.Gicquel, K.Mikusova, M.Jackson, P.M.Alzari.
 
  ABSTRACT  
 
Mycobacterial phosphatidylinositol mannosides (PIMs) and metabolically derived cell wall lipoglycans play important roles in host-pathogen interactions, but their biosynthetic pathways are poorly understood. Here we focus on Mycobacterium smegmatis PimA, an essential enzyme responsible for the initial mannosylation of phosphatidylinositol. The structure of PimA in complex with GDP-mannose shows the two-domain organization and the catalytic machinery typical of GT-B glycosyltransferases. PimA is an amphitrophic enzyme that binds mono-disperse phosphatidylinositol, but its transferase activity is stimulated by high concentrations of non-substrate anionic surfactants, indicating that the early stages of PIM biosynthesis involve lipid-water interfacial catalysis. Based on structural, calorimetric, and mutagenesis studies, we propose a model wherein PimA attaches to the membrane through its N-terminal domain, and this association leads to enzyme activation. Our results reveal a novel mode of phosphatidylinositol recognition and provide a template for the development of potential antimycobacterial compounds.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20400947 A.L.Lovering, L.Y.Lin, E.W.Sewell, T.Spreter, E.D.Brown, and N.C.Strynadka (2010).
Structure of the bacterial teichoic acid polymerase TagF provides insights into membrane association and catalysis.
  Nat Struct Mol Biol, 17, 582-589.
PDB codes: 3l7i 3l7j 3l7k 3l7l 3l7m
19929855 B.Absmanner, V.Schmeiser, M.Kämpf, and L.Lehle (2010).
Biochemical characterization, membrane association and identification of amino acids essential for the function of Alg11 from Saccharomyces cerevisiae, an alpha1,2-mannosyltransferase catalysing two sequential glycosylation steps in the formation of the lipid-linked core oligosaccharide.
  Biochem J, 426, 205-217.  
20393651 B.Cao, and S.J.Williams (2010).
Chemical approaches for the study of the mycobacterial glycolipids phosphatidylinositol mannosides, lipomannan and lipoarabinomannan.
  Nat Prod Rep, 27, 919-947.  
21154671 C.Luley-Goedl, and B.Nidetzky (2010).
Carbohydrate synthesis by disaccharide phosphorylases: reactions, catalytic mechanisms and application in the glycosciences.
  Biotechnol J, 5, 1324-1338.  
20696712 H.Song, W.Qian, H.Wang, and B.Qiu (2010).
Identification and functional characterization of the HpALG11 and the HpRFT1 genes involved in N-linked glycosylation in the methylotrophic yeast Hansenula polymorpha.
  Glycobiology, 20, 1665-1674.  
20843801 S.M.Batt, T.Jabeen, A.K.Mishra, N.Veerapen, K.Krumbach, L.Eggeling, G.S.Besra, and K.Fütterer (2010).
Acceptor substrate discrimination in phosphatidyl-myo-inositol mannoside synthesis: structural and mutational analysis of mannosyltransferase Corynebacterium glutamicum PimB'.
  J Biol Chem, 285, 37741-37752.
PDB codes: 3oka 3okc 3okp
  19729090 D.Kaur, M.E.Guerin, H.Skovierová, P.J.Brennan, and M.Jackson (2009).
Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis.
  Adv Appl Microbiol, 69, 23-78.  
19767390 H.M.Eriksson, P.Wessman, C.Ge, K.Edwards, and A.Wieslander (2009).
Massive formation of intracellular membrane vesicles in Escherichia coli by a monotopic membrane-bound lipid glycosyltransferase.
  J Biol Chem, 284, 33904-33914.  
19159314 J.M.Troutman, and B.Imperiali (2009).
Campylobacter jejuni PglH is a single active site processive polymerase that utilizes product inhibition to limit sequential glycosyl transfer reactions.
  Biochemistry, 48, 2807-2816.  
19638342 M.E.Guerin, D.Kaur, B.S.Somashekar, S.Gibbs, P.Gest, D.Chatterjee, P.J.Brennan, and M.Jackson (2009).
New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis.
  J Biol Chem, 284, 25687-25696.  
19520856 M.E.Guerin, F.Schaeffer, A.Chaffotte, P.Gest, D.Giganti, J.Korduláková, M.van der Woerd, M.Jackson, and P.M.Alzari (2009).
Substrate-induced conformational changes in the essential peripheral membrane-associated mannosyltransferase PimA from mycobacteria: implications for catalysis.
  J Biol Chem, 284, 21613-21625.  
18822375 B.Henrissat, G.Sulzenbacher, and Y.Bourne (2008).
Glycosyltransferases, glycoside hydrolases: surprise, surprise!
  Curr Opin Struct Biol, 18, 527-533.  
  18205830 C.Goedl, and B.Nidetzky (2008).
The phosphate site of trehalose phosphorylase from Schizophyllum commune probed by site-directed mutagenesis and chemical rescue studies.
  FEBS J, 275, 903-913.  
18712829 K.M.Ruane, G.J.Davies, and C.Martinez-Fleites (2008).
Crystal structure of a family GT4 glycosyltransferase from Bacillus anthracis ORF BA1558.
  Proteins, 73, 784-787.
PDB code: 2jjm
  19052376 K.Steiner, A.Wojciechowska, C.Schäffer, and J.H.Naismith (2008).
Purification, crystallization and preliminary crystallographic analysis of WsaF, an essential rhamnosyltransferase from Geobacillus stearothermophilus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1163-1165.  
18390549 M.W.Vetting, P.A.Frantom, and J.S.Blanchard (2008).
Structural and enzymatic analysis of MshA from Corynebacterium glutamicum: substrate-assisted catalysis.
  J Biol Chem, 283, 15834-15844.
PDB codes: 3c48 3c4q 3c4v
18852249 M.Zhou, Z.Peng, P.Fives-Taylor, and H.Wu (2008).
A conserved C-terminal 13-amino-acid motif of Gap1 is required for Gap1 function and necessary for the biogenesis of a serine-rich glycoprotein of Streptococcus parasanguinis.
  Infect Immun, 76, 5624-5631.  
18161725 P.H.Tam, G.S.Besra, and T.L.Lowary (2008).
Exploring the substrate specificity of a mycobacterial polyprenol monophosphomannose-dependent alpha-(1-->6)-mannosyltransferase.
  Chembiochem, 9, 267-278.  
18802637 Q.Fan, F.Huang, P.F.Leadlay, and J.B.Spencer (2008).
The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase.
  Org Biomol Chem, 6, 3306-3314.  
18826412 Y.Li, Y.Chen, X.Huang, M.Zhou, R.Wu, S.Dong, D.G.Pritchard, P.Fives-Taylor, and H.Wu (2008).
A conserved domain of previously unknown function in Gap1 mediates protein-protein interaction and is required for biogenesis of a serine-rich streptococcal adhesin.
  Mol Microbiol, 70, 1094-1104.  
  18453718 Z.Fulton, P.K.Crellin, R.Brammananth, L.Zaker-Tabrizi, R.L.Coppel, J.Rossjohn, and T.Beddoe (2008).
Expression, purification, crystallization and preliminary X-ray characterization of a putative glycosyltransferase of the GT-A fold found in mycobacteria.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 428-431.  
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.