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protein ligands metals links
Transferase PDB id
1nm2
Jmol
Contents
Protein chain
305 a.a. *
Ligands
ACY ×2
Metals
_NI
Waters ×108
* Residue conservation analysis
PDB id:
1nm2
Name: Transferase
Title: "Malonyl-coa:acp transacylase"
Structure: Malonyl coa:acyl carrier protein malonyltransfera chain: a. Fragment: malonyl-coa:acp transacylase. Engineered: yes
Source: Streptomyces coelicolor. Organism_taxid: 100226. Strain: a3(2). Gene: fabd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.197     R-free:   0.232
Authors: A.T.Keatinge-Clay,A.A.Shelat,D.F.Savage,S.Tsai,L.J.W.Miercke J.D.O'Connell Iii,C.Khosla,R.M.Stroud
Key ref:
A.T.Keatinge-Clay et al. (2003). Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure, 11, 147-154. PubMed id: 12575934 DOI: 10.1016/S0969-2126(03)00004-2
Date:
08-Jan-03     Release date:   21-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P72391  (P72391_STRCO) -  Malonyl CoA:acyl carrier protein malonyltransferase
Seq:
Struc: 		316 a.a.
305 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     4 terms  

 

 
DOI no: 10.1016/S0969-2126(03)00004-2 Structure 11:147-154 (2003)
PubMed id: 12575934  
 
 
Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase.
A.T.Keatinge-Clay, A.A.Shelat, D.F.Savage, S.C.Tsai, L.J.Miercke, J.D.O'Connell, C.Khosla, R.M.Stroud.
 
  ABSTRACT  
 
Malonyl-CoA:ACP transacylase (MAT), the fabD gene product of Streptomyces coelicolor A3(2), participates in both fatty acid and polyketide synthesis pathways, transferring malonyl groups that are used as extender units in chain growth from malonyl-CoA to pathway-specific acyl carrier proteins (ACPs). Here, the 2.0 A structure reveals an invariant arginine bound to an acetate that mimics the malonyl carboxylate and helps define the extender unit binding site. Catalysis may only occur when the oxyanion hole is formed through substrate binding, preventing hydrolysis of the acyl-enzyme intermediate. Macromolecular docking simulations with actinorhodin ACP suggest that the majority of the ACP docking surface is formed by a helical flap. These results should help to engineer polyketide synthases (PKSs) that produce novel polyketides.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Electron Density Maps of the Active Site(A) The 2F[o] - F[c] map contoured at 1.2 s. His201 and Ser97 form the catalytic dyad. The carboxylate of ACY 1 is bound to the invariant residues Gln9 and Arg122. ACY 1 and a water molecule suggest where the malonyl group binds. Met126 and Phe200 probably form a selectivity filter that rejects a-substituted malonyl groups.(B) Omit map of ACY 1 and ACY 2 contoured at 3.5 s.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 147-154) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20617244 M.D.Shepherd, M.K.Kharel, L.L.Zhu, S.G.van Lanen, and J.Rohr (2010).
Delineating the earliest steps of gilvocarcin biosynthesis: role of GilP and GilQ in starter unit specificity.
  Org Biomol Chem, 8, 3851-3856.  
20353188 Y.A.Chan, and M.G.Thomas (2010).
Recognition of (2S)-aminomalonyl-acyl carrier protein (ACP) and (2R)-hydroxymalonyl-ACP by acyltransferases in zwittermicin A biosynthesis.
  Biochemistry, 49, 3667-3677.  
20080587 Y.Shen, J.Liu, G.Estiu, B.Isin, Y.Y.Ahn, D.S.Lee, A.L.Barabási, V.Kapatral, O.Wiest, and Z.N.Oltvai (2010).
Blueprint for antimicrobial hit discovery targeting metabolic networks.
  Proc Natl Acad Sci U S A, 107, 1082-1087.  
19549604 G.Bunkoczi, S.Misquitta, X.Wu, W.H.Lee, A.Rojkova, G.Kochan, K.L.Kavanagh, U.Oppermann, and S.Smith (2009).
Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
  Chem Biol, 16, 667-675.  
19214500 G.R.Zhao, T.Luo, Y.J.Zhou, X.Jiang, B.Qiao, F.M.Yu, and Y.J.Yuan (2009).
fabC of Streptomyces lydicus involvement in the biosynthesis of streptolydigin.
  Appl Microbiol Biotechnol, 83, 305-313.  
19550039 M.J.Li, A.Q.Li, H.Xia, C.Z.Zhao, C.S.Li, S.B.Wan, Y.P.Bi, and X.J.Wang (2009).
Cloning and sequence analysis of putative type II fatty acid synthase genes from Arachis hypogaea L.
  J Biosci, 34, 227-238.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
19022176 G.Castaldo, J.Zucko, S.Heidelberger, D.Vujaklija, D.Hranueli, J.Cullum, P.Wattana-Amorn, M.P.Crump, J.Crosby, and P.F.Long (2008).
Proposed arrangement of proteins forming a bacterial type II polyketide synthase.
  Chem Biol, 15, 1156-1165.  
  19052370 J.W.Jung, S.Natarajan, H.Kim, Y.J.Ahn, S.Kim, J.G.Kim, B.M.Lee, and L.W.Kang (2008).
Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of malonyl-CoA-acyl carrier protein transacylase (FabD) from Xanthomonas oryzae pv. oryzae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1143-1145.  
19022178 N.B.Lopanik, J.A.Shields, T.J.Buchholz, C.M.Rath, J.Hothersall, M.G.Haygood, K.Håkansson, C.M.Thomas, and D.H.Sherman (2008).
In vivo and in vitro trans-acylation by BryP, the putative bryostatin pathway acyltransferase derived from an uncultured marine symbiont.
  Chem Biol, 15, 1175-1186.  
17653358 A.C.Mercer, and M.D.Burkart (2007).
The ubiquitous carrier protein--a window to metabolite biosynthesis.
  Nat Prod Rep, 24, 750-773.  
17268612 C.Hertweck, A.Luzhetskyy, Y.Rebets, and A.Bechthold (2007).
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Nat Prod Rep, 24, 162-190.  
17328673 C.Khosla, Y.Tang, A.Y.Chen, N.A.Schnarr, and D.E.Cane (2007).
Structure and mechanism of the 6-deoxyerythronolide B synthase.
  Annu Rev Biochem, 76, 195-221.  
18059524 D.M.Byers, and H.Gong (2007).
Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.
  Biochem Cell Biol, 85, 649-662.  
  17909282 H.Ghadbane, A.K.Brown, L.Kremer, G.S.Besra, and K.Fütterer (2007).
Structure of Mycobacterium tuberculosis mtFabD, a malonyl-CoA:acyl carrier protein transacylase (MCAT).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 831-835.
PDB code: 2qj3
17448991 I.B.Lomakin, Y.Xiong, and T.A.Steitz (2007).
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
  Cell, 129, 319-332.
PDB code: 2pff
17525466 L.Zhang, W.Liu, J.Xiao, T.Hu, J.Chen, K.Chen, H.Jiang, and X.Shen (2007).
Malonyl-CoA: acyl carrier protein transacylase from Helicobacter pylori: Crystal structure and its interaction with acyl carrier protein.
  Protein Sci, 16, 1184-1192.
PDB code: 2h1y
17431175 S.Jenni, M.Leibundgut, D.Boehringer, C.Frick, B.Mikolásek, and N.Ban (2007).
Structure of fungal fatty acid synthase and implications for iterative substrate shuttling.
  Science, 316, 254-261.
PDB codes: 2uv9 2uva 2uvb 2uvc
17466016 S.M.Ma, and Y.Tang (2007).
Biochemical characterization of the minimal polyketide synthase domains in the lovastatin nonaketide synthase LovB.
  FEBS J, 274, 2854-2864.  
17719492 Y.Tang, A.Y.Chen, C.Y.Kim, D.E.Cane, and C.Khosla (2007).
Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase.
  Chem Biol, 14, 931-943.
PDB code: 2qo3
16699188 C.Oefner, H.Schulz, A.D'Arcy, and G.E.Dale (2006).
Mapping the active site of Escherichia coli malonyl-CoA-acyl carrier protein transacylase (FabD) by protein crystallography.
  Acta Crystallogr D Biol Crystallogr, 62, 613-618.
PDB codes: 2g1h 2g2o 2g2y 2g2z
16597827 M.A.Johnson, W.Peti, T.Herrmann, I.A.Wilson, and K.Wüthrich (2006).
Solution structure of Asl1650, an acyl carrier protein from Anabaena sp. PCC 7120 with a variant phosphopantetheinylation-site sequence.
  Protein Sci, 15, 1030-1041.
PDB codes: 2afd 2afe
16513976 S.Jenni, M.Leibundgut, T.Maier, and N.Ban (2006).
Architecture of a fungal fatty acid synthase at 5 A resolution.
  Science, 311, 1263-1267.
PDB code: 2cdh
16513975 T.Maier, S.Jenni, and N.Ban (2006).
Architecture of mammalian fatty acid synthase at 4.5 A resolution.
  Science, 311, 1258-1262.
PDB code: 2cf2
15952903 S.W.White, J.Zheng, Y.M.Zhang, and Rock (2005).
The structural biology of type II fatty acid biosynthesis.
  Annu Rev Biochem, 74, 791-831.  
15286722 A.T.Keatinge-Clay, D.A.Maltby, K.F.Medzihradszky, C.Khosla, and R.M.Stroud (2004).
An antibiotic factory caught in action.
  Nat Struct Mol Biol, 11, 888-893.
PDB code: 1tqy
  12889743 C.D.Reeves (2003).
The enzymology of combinatorial biosynthesis.
  Crit Rev Biotechnol, 23, 95.  
14527946 Y.M.Zhang, B.Wu, J.Zheng, and C.O.Rock (2003).
Key residues responsible for acyl carrier protein and beta-ketoacyl-acyl carrier protein reductase (FabG) interaction.
  J Biol Chem, 278, 52935-52943.  
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 code is shown on the right.