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PDBsum entry 1lo9

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Hydrolase PDB id
1lo9
Jmol
Contents
Protein chain
140 a.a. *
Ligands
BCA
Waters ×15
* Residue conservation analysis
PDB id:
1lo9
Name: Hydrolase
Title: X-ray crystal structure of 4-hydroxybenzoyl coa thioesterase mutant d17n complexed with 4-hydroxybenzoyl coa
Structure: 4-hydroxybenzoyl-coa thioesterase. Chain: a. Engineered: yes. Mutation: yes
Source: Pseudomonas sp. Cbs3. Organism_taxid: 72586. Strain: cbs-3. Gene: 4hbt_psesp. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.148     R-free:   0.247
Authors: J.B.Thoden,H.M.Holden,Z.Zhuang,D.Dunaway-Mariano
Key ref:
J.B.Thoden et al. (2002). X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase. J Biol Chem, 277, 27468-27476. PubMed id: 11997398 DOI: 10.1074/jbc.M203904200
Date:
06-May-02     Release date:   13-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56653  (4HBT_PSEUC) -  4-hydroxybenzoyl-CoA thioesterase
Seq:
Struc:
141 a.a.
140 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.1.2.23  - 4-hydroxybenzoyl-CoA thioesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-hydroxybenzoyl-CoA + H2O = 4-hydroxybenzoate + CoA
4-hydroxybenzoyl-CoA
Bound ligand (Het Group name = BCA)
corresponds exactly
+ H(2)O
= 4-hydroxybenzoate
+ CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     hydrolase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M203904200 J Biol Chem 277:27468-27476 (2002)
PubMed id: 11997398  
 
 
X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase.
J.B.Thoden, H.M.Holden, Z.Zhuang, D.Dunaway-Mariano.
 
  ABSTRACT  
 
The metabolic pathway by which 4-chlorobenzoate is degraded to 4-hydroxybenzoate in the soil-dwelling microbe Pseudomonas sp. strain CBS-3 consists of three enzymes including 4-hydroxybenzoyl-CoA thioesterase. The structure of the unbound form of this thioesterase has been shown to contain the so-called "hot dog" fold with a large helix packed against a five-stranded anti-parallel beta-sheet. To address the manner in which the enzyme accommodates the substrate within the active site, two inhibitors have been synthesized, namely 4-hydroxyphenacyl-CoA and 4-hydroxybenzyl-CoA. Here we describe the structural analyses of the enzyme complexed with these two inhibitors determined and refined to 1.5 and 1.8 A resolution, respectively. These studies indicate that only one protein side chain, Ser(91), participates directly in ligand binding. All of the other interactions between the protein and the inhibitors are mediated through backbone peptidic NH groups, carbonyl oxygens, and/or solvents. The structures of the enzyme-inhibitor complexes suggest that both a hydrogen bond and the positive end of a helix dipole moment serve to polarize the electrons away from the carbonyl carbon of the acyl group, thereby making it more susceptible to nucleophilic attack. Additionally, these studies demonstrate that the carboxylate group of Asp(17) is approximately 3.2 A from the carbonyl carbon of the acyl group. To address the role of Asp(17), the structure of the site-directed mutant protein D17N with bound substrate has also been determined. Taken together, these investigations suggest that the reaction mechanism may proceed through an acyl enzyme intermediate.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Ribbon representation of one subunit of 4-hydroxybenzoyl-CoA thioesterase. All of the figures were prepared with the software package MOLSCRIPT (6). Cterm, C terminus; Nterm, N terminus.
Figure 5.
Fig. 5. The thioesterase active site with bound 4-hydroxybenzyl-CoA. For the sake of clarity only those residues located with 3.5 Å of the acyl pantetheine unit are shown in a. A superposition of the thioesterase active sites with bound 4-hydroxybenzyl-CoA (red) or 4-hydroxyphenacyl (black) is depicted in b.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 27468-27476) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20882276 B.E.Alber (2011).
Biotechnological potential of the ethylmalonyl-CoA pathway.
  Appl Microbiol Biotechnol, 89, 17-25.  
20506386 D.C.Cantu, Y.Chen, and P.J.Reilly (2010).
Thioesterases: a new perspective based on their primary and tertiary structures.
  Protein Sci, 19, 1281-1295.  
19170545 J.Cao, H.Xu, H.Zhao, W.Gong, and D.Dunaway-Mariano (2009).
The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition and catalysis illuminated by a structure and function based analysis.
  Biochemistry, 48, 1293-1304.
PDB code: 3f5o
19321747 J.R.Widhalm, C.van Oostende, F.Furt, and G.J.Basset (2009).
A dedicated thioesterase of the Hotdog-fold family is required for the biosynthesis of the naphthoquinone ring of vitamin K1.
  Proc Natl Acad Sci U S A, 106, 5599-5603.  
19473548 L.S.Pidugu, K.Maity, K.Ramaswamy, N.Surolia, and K.Suguna (2009).
Analysis of proteins with the 'hot dog' fold: prediction of function and identification of catalytic residues of hypothetical proteins.
  BMC Struct Biol, 9, 37.  
19357082 M.Kotaka, R.Kong, I.Qureshi, Q.S.Ho, H.Sun, C.W.Liew, L.P.Goh, P.Cheung, Y.Mu, J.Lescar, and Z.X.Liang (2009).
Structure and catalytic mechanism of the thioesterase CalE7 in enediyne biosynthesis.
  J Biol Chem, 284, 15739-15749.
PDB code: 2w3x
19622860 T.Hosaka, K.Murayama, M.Kato-Murayama, A.Urushibata, R.Akasaka, T.Terada, M.Shirouzu, S.Kuramitsu, and S.Yokoyama (2009).
Structure of the putative thioesterase protein TTHA1846 from Thermus thermophilus HB8 complexed with coenzyme A and a zinc ion.
  Acta Crystallogr D Biol Crystallogr, 65, 767-776.
PDB code: 2cye
19303060 T.Yokoyama, K.J.Choi, A.M.Bosch, and H.J.Yeo (2009).
Structure and function of a Campylobacter jejuni thioesterase Cj0915, a hexameric hot dog fold enzyme.
  Biochim Biophys Acta, 1794, 1073-1081.
PDB code: 3d6l
18338382 A.Angelini, L.Cendron, S.Goncalves, G.Zanotti, and L.Terradot (2008).
Structural and enzymatic characterization of HP0496, a YbgC thioesterase from Helicobacter pylori.
  Proteins, 72, 1212-1221.
PDB code: 2pzh
19898606 M.Chruszcz, M.D.Zimmerman, S.Wang, K.D.Koclega, H.Zheng, E.Evdokimova, M.Kudritska, M.Cymborowski, A.Savchenko, A.Edwards, and W.Minor (2008).
Function-biased choice of additives for optimization of protein crystallization - the case of the putative thioesterase PA5185 from Pseudomonas aeruginosa PAO1.
  Cryst Growth Des, 8, 4054-4061.
PDB codes: 2av9 2o5u 2o6b 2o6t 2o6u
18835274 T.Yokoyama, S.Paek, C.P.Ewing, P.Guerry, and H.J.Yeo (2008).
Structure of a sigma28-regulated nonflagellar virulence protein from Campylobacter jejuni.
  J Mol Biol, 384, 364-376.
PDB code: 3bnv
17524985 F.Wang, R.Langley, G.Gulten, L.Wang, and J.C.Sacchettini (2007).
Identification of a type III thioesterase reveals the function of an operon crucial for Mtb virulence.
  Chem Biol, 14, 543-551.
PDB code: 2pfc
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
16932747 G.E.Schujman, M.Guerin, A.Buschiazzo, F.Schaeffer, L.I.Llarrull, G.Reh, A.J.Vila, P.M.Alzari, and D.de Mendoza (2006).
Structural basis of lipid biosynthesis regulation in Gram-positive bacteria.
  EMBO J, 25, 4074-4083.
PDB codes: 2f3x 2f41
15987908 A.Castell, P.Johansson, T.Unge, T.A.Jones, and K.Bäckbro (2005).
Rv0216, a conserved hypothetical protein from Mycobacterium tuberculosis that is essential for bacterial survival during infection, has a double hotdog fold.
  Protein Sci, 14, 1850-1862.
PDB code: 2bi0
15307895 S.C.Dillon, and A.Bateman (2004).
The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases.
  BMC Bioinformatics, 5, 109.  
14997554 Y.Tajika, N.Sakai, Y.Tanaka, M.Yao, N.Watanabe, and I.Tanaka (2004).
Crystal structure of conserved protein PH1136 from Pyrococcus horikoshii.
  Proteins, 55, 210-213.
PDB code: 1ixl
14702308 Z.Zhuang, F.Song, H.Takami, and D.Dunaway-Mariano (2004).
The BH1999 protein of Bacillus halodurans C-125 is gentisyl-coenzyme A thioesterase.
  J Bacteriol, 186, 393-399.  
12732540 Z.Zhuang, K.H.Gartemann, R.Eichenlaub, and D.Dunaway-Mariano (2003).
Characterization of the 4-hydroxybenzoyl-coenzyme A thioesterase from Arthrobacter sp. strain SU.
  Appl Environ Microbiol, 69, 2707-2711.  
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.