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PDBsum entry 2qo3

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
2qo3
Jmol
Contents
Protein chains
869 a.a. *
Ligands
ACT ×2
CER ×2
Metals
_CL ×2
Waters ×194
* Residue conservation analysis
PDB id:
2qo3
Name: Transferase
Title: Crystal structure of [ks3][at3] didomain from module 3 of 6- deoxyerthronolide b synthase
Structure: Eryaii erythromycin polyketide synthase modules 3 chain: a, b. Fragment: ketosynthase-acyltransferase didomain of didomain synonym: 6 deoxyerythronolide b synthase. Engineered: yes
Source: Saccharopolyspora erythraea. Organism_taxid: 1836. Gene: eryaii. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.59Å     R-factor:   0.217     R-free:   0.268
Authors: C.Khosla,E.D.Cane,Y.Tang,Y.A.Chen,C.Y.Kim
Key ref: Y.Tang et al. (2007). Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem Biol, 14, 931-943. PubMed id: 17719492
Date:
19-Jul-07     Release date:   04-Sep-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q03132  (ERYA2_SACER) -  Erythronolide synthase, modules 3 and 4
Seq:
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Seq:
Struc:
3567 a.a.
869 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     2 terms  

 

 
Chem Biol 14:931-943 (2007)
PubMed id: 17719492  
 
 
Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase.
Y.Tang, A.Y.Chen, C.Y.Kim, D.E.Cane, C.Khosla.
 
  ABSTRACT  
 
We report the 2.6 A X-ray crystal structure of a 190 kDa homodimeric fragment from module 3 of the 6-deoxyerthronolide B synthase covalently bound to the inhibitor cerulenin. The structure shows two well-organized interdomain linker regions in addition to the full-length ketosynthase (KS) and acyltransferase (AT) domains. Analysis of the substrate-binding site of the KS domain suggests that a loop region at the homodimer interface influences KS substrate specificity. We also describe a model for the interaction of the catalytic domains with the acyl carrier protein (ACP) domain. The ACP is proposed to dock within a deep cleft between the KS and AT domains, with interactions that span both the KS homodimer and AT domain. In conjunction with other recent data, our results provide atomic resolution pictures of several catalytically relevant protein interactions in this remarkable family of modular megasynthases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20152156 D.L.Akey, J.R.Razelun, J.Tehranisa, D.H.Sherman, W.H.Gerwick, and J.L.Smith (2010).
Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway.
  Structure, 18, 94.
PDB codes: 3kg6 3kg7 3kg8 3kg9
19921859 F.T.Wong, A.Y.Chen, D.E.Cane, and C.Khosla (2010).
Protein-protein recognition between acyltransferases and acyl carrier proteins in multimodular polyketide synthases.
  Biochemistry, 49, 95.  
20444870 S.Anand, M.V.Prasad, G.Yadav, N.Kumar, J.Shehara, M.Z.Ansari, and D.Mohanty (2010).
SBSPKS: structure based sequence analysis of polyketide synthases.
  Nucleic Acids Res, 38, W487-W496.  
21127271 S.Kapur, A.Y.Chen, D.E.Cane, and C.Khosla (2010).
Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase.
  Proc Natl Acad Sci U S A, 107, 22066-22071.  
20731893 T.Maier, M.Leibundgut, D.Boehringer, and N.Ban (2010).
Structure and function of eukaryotic fatty acid synthases.
  Q Rev Biophys, 43, 373-422.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
19217343 C.Khosla, S.Kapur, and D.E.Cane (2009).
Revisiting the modularity of modular polyketide synthases.
  Curr Opin Chem Biol, 13, 135-143.  
19151726 E.J.Brignole, S.Smith, and F.J.Asturias (2009).
Conformational flexibility of metazoan fatty acid synthase enables catalysis.
  Nat Struct Mol Biol, 16, 190-197.  
19551180 J.L.Meier, and M.D.Burkart (2009).
The chemical biology of modular biosynthetic enzymes.
  Chem Soc Rev, 38, 2012-2045.  
19507202 M.Tosin, D.Spiteller, and J.B.Spencer (2009).
Malonyl carba(dethia)- and malonyl oxa(dethia)-coenzyme A as tools for trapping polyketide intermediates.
  Chembiochem, 10, 1714-1723.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
18357594 K.J.Weissman, and R.Müller (2008).
Protein-protein interactions in multienzyme megasynthetases.
  Chembiochem, 9, 826-848.  
18348128 L.Tran, M.Tosin, J.B.Spencer, P.F.Leadlay, and K.J.Weissman (2008).
Covalent linkage mediates communication between ACP and TE domains in modular polyketide synthases.
  Chembiochem, 9, 905-915.  
18948193 M.Leibundgut, T.Maier, S.Jenni, and N.Ban (2008).
The multienzyme architecture of eukaryotic fatty acid synthases.
  Curr Opin Struct Biol, 18, 714-725.  
18243693 S.Kapur, A.Worthington, Y.Tang, D.E.Cane, M.D.Burkart, and C.Khosla (2008).
Mechanism based protein crosslinking of domains from the 6-deoxyerythronolide B synthase.
  Bioorg Med Chem Lett, 18, 3034-3038.  
18772430 T.Maier, M.Leibundgut, and N.Ban (2008).
The crystal structure of a mammalian fatty acid synthase.
  Science, 321, 1315-1322.
PDB codes: 2vz8 2vz9
17656315 A.Y.Chen, D.E.Cane, and C.Khosla (2007).
Structure-based dissociation of a type I polyketide synthase module.
  Chem Biol, 14, 784-792.  
17918944 R.Castonguay, W.He, A.Y.Chen, C.Khosla, and D.E.Cane (2007).
Stereospecificity of ketoreductase domains of the 6-deoxyerythronolide B synthase.
  J Am Chem Soc, 129, 13758-13769.  
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.