PDBsum entry 1l1e

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Transferase PDB id
Protein chains
272 a.a. *
CO3 ×2
SAH ×2
Waters ×200
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of mycolic acid cyclopropane synthase pcaa complexed with s-adenosyl-l-homocysteine
Structure: Mycolic acid synthase. Chain: a, b. Synonym: pcaa cyclopropane synthase. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: pcaa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.00Å     R-factor:   0.222     R-free:   0.270
Authors: C.-C.Huang,C.V.Smith,M.S.Glickman,W.R.Jacobs Jr., J.C.Sacchettini,Tb Structural Genomics Consortium (Tbsgc)
Key ref:
C.C.Huang et al. (2002). Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis. J Biol Chem, 277, 11559-11569. PubMed id: 11756461 DOI: 10.1074/jbc.M111698200
15-Feb-02     Release date:   06-Mar-02    
Go to PROCHECK summary

Protein chains
P9WPB3  (CMAS3_MYCTU) -  Cyclopropane mycolic acid synthase 3
287 a.a.
272 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Cyclopropane-fatty-acyl-phospholipid synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + phospholipid olefinic fatty acid = S-adenosyl- L-homocysteine + phospholipid cyclopropane fatty acid
+ phospholipid olefinic fatty acid
= S-adenosyl- L-homocysteine
+ phospholipid cyclopropane fatty acid
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     lipid metabolic process   3 terms 
  Biochemical function     transferase activity     3 terms  


DOI no: 10.1074/jbc.M111698200 J Biol Chem 277:11559-11569 (2002)
PubMed id: 11756461  
Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis.
C.C.Huang, C.V.Smith, M.S.Glickman, W.R.Jacobs, J.C.Sacchettini.
Mycolic acids are major components of the cell wall of Mycobacterium tuberculosis. Several studies indicate that functional groups in the acyl chain of mycolic acids are important for pathogenesis and persistence. There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of mycolic acids. To derive information on the specificity and enzyme mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold similar to other methyltransferases with the location and interactions with the cofactor S-adenosyl-l-methionine conserved. The structures of the ternary complexes demonstrate the position of the mycolic acid substrate binding site. Close examination of the active site reveals electron density that we believe represents a bicarbonate ion. The structures support the hypothesis that these enzymes catalyze methyl transfer via a carbocation mechanism in which the bicarbonate ion acts as a general base. In addition, comparison of the enzyme structures reveals a possible mechanism for substrate specificity. These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria.
  Selected figure(s)  
Figure 3.
Fig. 3. Structure of apoCmaA1. a, superimposition of C[ ]atoms of structures of apoCmaA1 (gray) and CmaAl-SAH-DDDMAB (blue) using residues 20-170. Residues 136-145 and residues 170-210 of apoCmaA1 are colored in green. b, comparison of the active site cavities in apoCmaA1 and CmaAl-SAH-DDDMAB.
Figure 4.
Fig. 4. a, interactions between cofactor SAH and CmaA1. The detailed interactions are also listed in Table II. The figure was prepared using LIGPLOT(54). b, interactions between 7 amino acid insertions (residues 153-159) of CmaA2 (orange) and the N terminus compared with CmaA1 (blue). c, active site architecture. SAH and DDDMAB are shown in green. Residues 136-140 are shown in orange. DDDMAB in CmaA2-SAH-DDDMAB structure is superimposed with CmaA1-SAH-DDDMAB structure and is shown in gray. The bicarbonate ion in the active site is shown interacting with His-167, Cys-35, and Glu-140. The carbocation intermediate of the reaction mechanism may be stabilized by cation- interactions during catalysis, specifically by the aromatic ring of the Tyr-33.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 11559-11569) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20686769 T.Jiang, Y.Zhan, M.Sun, S.Liu, S.Zang, Y.Ma, and Y.Xin (2011).
The Novel Responses of Ethambutol Against Mycobacterium smegmatis mc(2)155 Revealed by Proteomics Analysis.
  Curr Microbiol, 62, 341-345.  
21209917 G.Bashiri, A.M.Rehan, D.R.Greenwood, J.M.Dickson, and E.N.Baker (2010).
Metabolic engineering of cofactor F420 production in Mycobacterium smegmatis.
  PLoS One, 5, e15803.  
20359198 R.S.Rowlett, K.M.Hoffmann, H.Failing, M.M.Mysliwiec, and D.Samardzic (2010).
Evidence for a bicarbonate "escort" site in Haemophilus influenzae beta-carbonic anhydrase .
  Biochemistry, 49, 3640-3647.
PDB codes: 3e2x 3e31 3e3f 3e3g 3e3i
20179338 T.C.Terwilliger (2010).
Rapid model building of alpha-helices in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 268-275.  
20179339 T.C.Terwilliger (2010).
Rapid model building of beta-sheets in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 276-284.  
20179340 T.C.Terwilliger (2010).
Rapid chain tracing of polypeptide backbones in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 285-294.  
19183278 A.Alahari, L.Alibaud, X.Trivelli, R.Gupta, G.Lamichhane, R.C.Reynolds, W.R.Bishai, Y.Guerardel, and L.Kremer (2009).
Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis.
  Mol Microbiol, 71, 1263-1277.  
19477414 D.Barkan, Z.Liu, J.C.Sacchettini, and M.S.Glickman (2009).
Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis.
  Chem Biol, 16, 499-509.  
18623062 J.G.McCoy, L.J.Bailey, Y.H.Ng, C.A.Bingman, R.Wrobel, A.P.Weber, B.G.Fox, and G.N.Phillips (2009).
Discovery of sarcosine dimethylglycine methyltransferase from Galdieria sulphuraria.
  Proteins, 74, 368-377.  
19439410 J.Vaubourgeix, F.Bardou, F.Boissier, S.Julien, P.Constant, O.Ploux, M.Daffé, A.Quémard, and L.Mourey (2009).
S-adenosyl-N-decyl-aminoethyl, a potent bisubstrate inhibitor of mycobacterium tuberculosis mycolic acid methyltransferases.
  J Biol Chem, 284, 19321-19330.  
19202086 L.Saborido Basconcillo, R.Zaheer, T.M.Finan, and B.E.McCarry (2009).
Cyclopropane fatty acyl synthase in Sinorhizobium meliloti.
  Microbiology, 155, 373-385.  
19465773 T.C.Terwilliger, P.D.Adams, R.J.Read, A.J.McCoy, N.W.Moriarty, R.W.Grosse-Kunstleve, P.V.Afonine, P.H.Zwart, and L.W.Hung (2009).
Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard.
  Acta Crystallogr D Biol Crystallogr, 65, 582-601.  
  18997344 A.Jain, J.Ziegler, D.K.Liscombe, P.J.Facchini, P.A.Tucker, and S.Panjikar (2008).
Purification, crystallization and X-ray diffraction analysis of pavine N-methyltransferase from Thalictrum flavum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1066-1069.  
18953716 M.Y.Lin, and T.H.Ottenhoff (2008).
Not to wake a sleeping giant: new insights into host-pathogen interactions identify new targets for vaccination against latent Mycobacterium tuberculosis infection.
  Biol Chem, 389, 497-511.  
18563465 P.Jayasimha, and W.D.Nes (2008).
Photoaffinity labeling and mutational analysis of 24-C-sterol methyltransferase defines the AdoMet binding site.
  Lipids, 43, 681-693.  
18502766 S.Singh, J.G.McCoy, C.Zhang, C.A.Bingman, G.N.Phillips, and J.S.Thorson (2008).
Structure and mechanism of the rebeccamycin sugar 4'-O-methyltransferase RebM.
  J Biol Chem, 283, 22628-22636.
PDB code: 3bus
18094751 A.Alahari, X.Trivelli, Y.Guérardel, L.G.Dover, G.S.Besra, J.C.Sacchettini, R.C.Reynolds, G.D.Coxon, and L.Kremer (2007).
Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in Mycobacteria.
  PLoS ONE, 2, e1343.  
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.  
17668294 E.N.Baker (2007).
Structural genomics as an approach towards understanding the biology of tuberculosis.
  J Struct Funct Genomics, 8, 57-65.  
17660248 M.Graña, A.Haouz, A.Buschiazzo, I.Miras, A.Wehenkel, V.Bondet, W.Shepard, F.Schaeffer, S.T.Cole, and P.M.Alzari (2007).
The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria.
  Protein Sci, 16, 1896-1904.
PDB codes: 2ckd 2uyo 2uyq
17898899 P.H.Buist (2007).
Exotic biomodification of fatty acids.
  Nat Prod Rep, 24, 1110-1127.  
16923914 M.Gulmezian, H.Zhang, G.T.Javor, and C.F.Clarke (2006).
Genetic evidence for an interaction of the UbiG O-methyltransferase with UbiX in Escherichia coli coenzyme Q biosynthesis.
  J Bacteriol, 188, 6435-6439.  
16929102 R.Pai, J.Sacchettini, and T.Ioerger (2006).
Identifying non-crystallographic symmetry in protein electron-density maps: a feature-based approach.
  Acta Crystallogr D Biol Crystallogr, 62, 1012-1021.  
17057345 T.D.Romo, J.C.Sacchettini, and T.R.Ioerger (2006).
Improving amino-acid identification, fit and C(alpha) prediction using the Simplex method in automated model building.
  Acta Crystallogr D Biol Crystallogr, 62, 1401-1406.  
17005277 T.L.Sorensen, K.E.McAuley, R.Flaig, and E.M.Duke (2006).
New light for science: synchrotron radiation in structural medicine.
  Trends Biotechnol, 24, 500-508.  
16478688 V.L.Arcus, J.S.Lott, J.M.Johnston, and E.N.Baker (2006).
The potential impact of structural genomics on tuberculosis drug discovery.
  Drug Discov Today, 11, 28-34.  
16322509 Y.Liu, P.Srivilai, S.Loos, M.Aebi, and U.Kües (2006).
An essential gene for fruiting body initiation in the basidiomycete Coprinopsis cinerea is homologous to bacterial cyclopropane fatty acid synthase genes.
  Genetics, 172, 873-884.  
16225687 P.Z.Kozbial, and A.R.Mushegian (2005).
Natural history of S-adenosylmethionine-binding proteins.
  BMC Struct Biol, 5, 19.  
14977982 D.E.Geiman, D.Kaushal, C.Ko, S.Tyagi, Y.C.Manabe, B.G.Schroeder, R.D.Fleischmann, N.E.Morrison, P.J.Converse, P.Chen, and W.R.Bishai (2004).
Attenuation of late-stage disease in mice infected by the Mycobacterium tuberculosis mutant lacking the SigF alternate sigma factor and identification of SigF-dependent genes by microarray analysis.
  Infect Immun, 72, 1733-1745.  
15606764 F.Courtois, C.Guérard, X.Thomas, and O.Ploux (2004).
Escherichia coli cyclopropane fatty acid synthase.
  Eur J Biochem, 271, 4769-4778.  
15109786 L.G.Dover, A.M.Cerdeño-Tárraga, M.J.Pallen, J.Parkhill, and G.S.Besra (2004).
Comparative cell wall core biosynthesis in the mycolated pathogens, Mycobacterium tuberculosis and Corynebacterium diphtheriae.
  FEMS Microbiol Rev, 28, 225-250.  
15306017 T.A.Gould, H.P.Schweizer, and M.E.Churchill (2004).
Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI.
  Mol Microbiol, 53, 1135-1146.
PDB code: 1ro5
12809568 B.J.Berger, and M.H.Knodel (2003).
Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis.
  BMC Microbiol, 3, 12.  
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
14646078 V.Reddy, S.M.Swanson, B.Segelke, K.A.Kantardjieff, J.C.Sacchettini, and B.Rupp (2003).
Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service.
  Acta Crystallogr D Biol Crystallogr, 59, 2200-2210.  
12732555 Y.Zhao, L.A.Hindorff, A.Chuang, M.Monroe-Augustus, M.Lyristis, M.L.Harrison, F.B.Rudolph, and G.N.Bennett (2003).
Expression of a cloned cyclopropane fatty acid synthase gene reduces solvent formation in Clostridium acetobutylicum ATCC 824.
  Appl Environ Microbiol, 69, 2831-2841.  
12454463 T.R.Ioerger, and J.C.Sacchettini (2002).
Automatic modeling of protein backbones in electron-density maps via prediction of Calpha coordinates.
  Acta Crystallogr D Biol Crystallogr, 58, 2043-2054.  
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.