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PDBsum entry 1kux
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Transferase PDB id
1kux

 

 

 

 

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Contents
Protein chain
166 a.a. *
Ligands
CA3
Waters ×160
* Residue conservation analysis
PDB id:
1kux
Name: Transferase
Title: X-ray crystallographic studies of serotonin n-acetyltransferase catalysis and inhibition
Structure: Serotonin n-acetyltransferase. Chain: a. Synonym: arylalkylamine n-acetyltransferase. Aralkylamine n- acetyltransferase. Aa-nat. Serotonin acetylase. Engineered: yes. Mutation: yes
Source: Ovis aries. Sheep. Organism_taxid: 9940. Gene: u29663. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.197     R-free:   0.225
Authors: E.Wolf,J.De Angelis,E.M.Khalil,P.A.Cole,S.K.Burley
Key ref:
E.Wolf et al. (2002). X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition. J Mol Biol, 317, 215-224. PubMed id: 11902838 DOI: 10.1006/jmbi.2001.5371
Date:
22-Jan-02     Release date:   22-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Q29495  (SNAT_SHEEP) -  Serotonin N-acetyltransferase from Ovis aries
Seq:
Struc: 		207 a.a.
166 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.87  - aralkylamine N-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 2-arylethylamine + acetyl-CoA = an N-acetyl-2-arylethylamine + CoA + H+
2-arylethylamine
 +
acetyl-CoA
Bound ligand (Het Group name = CA3)
matches with 74.63% similarity 		= N-acetyl-2-arylethylamine
 + CoA
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2001.5371 J Mol Biol 317:215-224 (2002)
PubMed id: 11902838  
 
 
X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition.
E.Wolf, J.De Angelis, E.M.Khalil, P.A.Cole, S.K.Burley.
 
  ABSTRACT  
 
The structure of serotonin N-acetyltransferase (also known as arylalkylamine N-acetyltransferase; AANAT) bound to a potent bisubstrate analog inhibitor has been determined at 2.0 A resolution using a two-edge (Se, Br) multiwavelength anomalous diffraction (MAD) experiment. This acetyl-CoA dependent enzyme is a member of the GCN5-related family of N-acetyltransferases (GNATs), which share four conserved sequence motifs (A-D). In serotonin N-acetyltransferase, motif A adopts an alpha/beta conformation characteristic of the phylogenetically invariant cofactor binding site seen in all previously characterized GNATs. Motif B displays a significantly lower level of conservation among family members, giving rise to a novel alpha/beta structure for the serotonin binding slot. Utilization of a brominated CoA-S-acetyl-tryptamine-bisubstrate analog inhibitor and the MAD method permitted conclusive identification of two radically different conformations for the tryptamine moiety in the catalytic site (cis and trans). A second high-resolution X-ray structure of the enzyme bound to a bisubstrate analog inhibitor, with a longer tether between the acetyl-CoA and tryptamine moieties, demonstrates only the trans conformation. Given a previous proposal that AANAT can catalyze an alkyltransferase reaction in a conformationally altered active site relative to its acetyltransferase activity, it is possible that the two conformations of the bisubstrate analog observed crystallographically correspond to these alternative reaction pathways. Our findings may ultimately lead to the design of analogs with improved AANAT inhibitory properties for in vivo applications.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Enzyme-catalyzed reactions and inhibitors for serotonin N-acetyltransferase. (a) Serotonin N-acetyltransferase-catalyzed reaction between serotonin and acetyl-CoA. (b) Alkyl transfer reaction between CoASH and N-bromoacetyltryptamine. (c) Bisubstrate analog inhibitors 1, 2, and 3. 		Figure 4.
Figure 4. Overlay of compounds 1 and 3 in the active site of AANAT. Left: a stereodrawing of compounds 1 (green) and 3 (red) drawn as atomic stick figures with selected atoms labeled. Right: the atomic numbering scheme for the tryptamine moieties of compounds 1, 2, and 3.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 317, 215-224) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18362150 J.Pavlicek, S.L.Coon, S.Ganguly, J.L.Weller, S.A.Hassan, D.L.Sackett, and D.C.Klein (2008).
Evidence that proline focuses movement of the floppy loop of arylalkylamine N-acetyltransferase (EC 2.3.1.87).
  J Biol Chem, 283, 14552-14558.  
18596200 M.W.Vetting, D.C.Bareich, M.Yu, and J.S.Blanchard (2008).
Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for N(alpha)-acetylation of ribosomal protein S18.
  Protein Sci, 17, 1781-1790.
PDB codes: 2cnm 2cns 2cnt
18373682 T.Kotani, and H.Takagi (2008).
Identification of amino acid residues essential for the yeast N-acetyltransferase Mpr1 activity by site-directed mutagenesis.
  FEMS Yeast Res, 8, 607-614.  
17164235 D.C.Klein (2007).
Arylalkylamine N-acetyltransferase: "the Timezyme".
  J Biol Chem, 282, 4233-4237.  
17924613 L.M.Szewczuk, S.A.Saldanha, S.Ganguly, E.M.Bowers, M.Javoroncov, B.Karanam, J.C.Culhane, M.A.Holbert, D.C.Klein, R.Abagyan, and P.A.Cole (2007).
De novo discovery of serotonin N-acetyltransferase inhibitors.
  J Med Chem, 50, 5330-5338.  
16356930 C.A.Toleman, A.J.Paterson, and J.E.Kudlow (2006).
The histone acetyltransferase NCOAT contains a zinc finger-like motif involved in substrate recognition.
  J Biol Chem, 281, 3918-3925.  
16855251 M.N.Hung, E.Rangarajan, C.Munger, G.Nadeau, T.Sulea, and A.Matte (2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
  J Bacteriol, 188, 5606-5617.
PDB codes: 2fs5 2ft0
16206301 F.Gao, X.Yan, O.M.Baettig, A.M.Berghuis, and K.Auclair (2005).
Regio- and chemoselective 6'-N-derivatization of aminoglycosides: bisubstrate inhibitors as probes to study aminoglycoside 6'-N-acetyltransferases.
  Angew Chem Int Ed Engl, 44, 6859-6862.  
15992934 J.A.Boutin, V.Audinot, G.Ferry, and P.Delagrange (2005).
Molecular tools to study melatonin pathways and actions.
  Trends Pharmacol Sci, 26, 412-419.  
14717709 G.Ferry, C.Ubeaud, J.Mozo, C.Péan, P.Hennig, M.Rodriguez, C.Scoul, A.Bonnaud, O.Nosjean, J.P.Galizzi, P.Delagrange, P.Renard, J.P.Volland, S.Yous, D.Lesieur, and J.A.Boutin (2004).
New substrate analogues of human serotonin N-acetyltransferase produce in situ specific and potent inhibitors.
  Eur J Biochem, 271, 418-428.  
12566434 D.D.Boehr, S.I.Jenkins, and G.D.Wright (2003).
The molecular basis of the expansive substrate specificity of the antibiotic resistance enzyme aminoglycoside acetyltransferase-6'-aminoglycoside phosphotransferase-2". The role of ASP-99 as an active site base important for acetyl transfer.
  J Biol Chem, 278, 12873-12880.  
12391296 A.N.Poux, M.Cebrat, C.M.Kim, P.A.Cole, and R.Marmorstein (2002).
Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor.
  Proc Natl Acad Sci U S A, 99, 14065-14070.
PDB code: 1m1d
11884405 K.A.Scheibner, J.De Angelis, S.K.Burley, and P.A.Cole (2002).
Investigation of the roles of catalytic residues in serotonin N-acetyltransferase.
  J Biol Chem, 277, 18118-18126.
PDB code: 1l0c
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.

 

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