PDBsum entry 1jkm

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Serine hydrolase PDB id
Protein chains
358 a.a. *
Waters ×531
* Residue conservation analysis
PDB id:
Name: Serine hydrolase
Title: Brefeldin a esterase, a bacterial homologue of human hormone sensitive lipase
Structure: Brefeldin a esterase. Chain: a, b. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Cell_line: 293. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
1.85Å     R-factor:   0.170     R-free:   0.206
Authors: Y.Wei,A.J.Contreras,P.Sheffield,T.Osterlund,U.Derewenda, U.O.Matern,Z.S.Derewenda
Key ref:
Y.Wei et al. (1999). Crystal structure of brefeldin A esterase, a bacterial homolog of the mammalian hormone-sensitive lipase. Nat Struct Biol, 6, 340-345. PubMed id: 10201402 DOI: 10.1038/7576
04-Feb-98     Release date:   16-Feb-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O68884  (O68884_BACIU) -  Brefeldin A esterase
372 a.a.
358 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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


DOI no: 10.1038/7576 Nat Struct Biol 6:340-345 (1999)
PubMed id: 10201402  
Crystal structure of brefeldin A esterase, a bacterial homolog of the mammalian hormone-sensitive lipase.
Y.Wei, J.A.Contreras, P.Sheffield, T.Osterlund, U.Derewenda, R.E.Kneusel, U.Matern, C.Holm, Z.S.Derewenda.
Brefeldin A esterase (BFAE), a detoxifying enzyme isolated from Bacillus subtilis, hydrolyzes and inactivates BFA, a potent fungal inhibitor of intracellular vesicle-dependent secretory transport and poliovirus RNA replication. We have solved the crystal structure of BFAE and we discovered that the previously reported amino acid sequence was in serious error due to frame shifts in the cDNA sequence. The correct sequence, inferred from the experimentally phased electron density map, revealed that BFAE is a homolog of the mammalian hormone sensitive lipase (HSL). It is a canonical alpha/beta hydrolase with two insertions forming the substrate binding pocket. The enzyme contains a lipase-like catalytic triad, Ser 202, Asp 308 and His 338, consistent with mutational studies that implicate the homologous Ser 424, Asp 693 and His 723 in the catalytic triad in human HSL.
  Selected figure(s)  
Figure 2.
Figure 2. green depicts the N-terminal fragment containing two helices( 1, 30−41 and 2, 56−78); the central -pleated sheet is shown in yellow ( 1, 89−98; 2, 102−111; 3, 119−127; 4, 151−158; 5, 194−201; 6, 226−231; 7, 299−306; 8, 327−334) while the -helices of the core fragment are shown in pale blue ( 3, 137−149; 4, 171−188; 5, 203−218; 9, 310−324; 10, 349−370); the red color denotes an insertion in the fifth connecting loop on the carboxyl edge of the sheet ( 6, 241−248; 7, 262−273; 8, 290−295); the three active site residues are shown in full. b, A schematic representation of the fold showing the canonical / hydrolase core. The color scheme corresponds to that in (a). c, C trace in stereo.
Figure 3.
Figure 3. a, The vicinity of the catalytic site in BFAE. The key residues are labeled and the hydrogen bonds are shown using broken lines. b, A model of the catalytic site in HSL based on the BFAE structure.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 340-345) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20834152 B.Bunterngsook, P.Kanokratana, T.Thongaram, S.Tanapongpipat, T.Uengwetwanit, S.Rachdawong, T.Vichitsoonthonkul, and L.Eurwilaichitr (2010).
Identification and characterization of lipolytic enzymes from a peat-swamp forest soil metagenome.
  Biosci Biotechnol Biochem, 74, 1848-1854.  
20170513 M.Widmann, P.B.Juhl, and J.Pleiss (2010).
Structural classification by the Lipase Engineering Database: a case study of Candida antarctica lipase A.
  BMC Genomics, 11, 123.  
19544040 M.Levisson, J.van der Oost, and S.W.Kengen (2009).
Carboxylic ester hydrolases from hyperthermophiles.
  Extremophiles, 13, 567-581.  
19304850 S.Montoro-García, I.Martínez-Martínez, J.Navarro-Fernández, H.Takami, F.García-Carmona, and A.Sánchez-Ferrer (2009).
Characterization of a novel thermostable carboxylesterase from Geobacillus kaustophilus HTA426 shows the existence of a new carboxylesterase family.
  J Bacteriol, 191, 3076-3085.  
18252723 A.K.Ghosh, G.Ramakrishnan, and R.Rajasekharan (2008).
YLR099C (ICT1) encodes a soluble Acyl-CoA-dependent lysophosphatidic acid acyltransferase responsible for enhanced phospholipid synthesis on organic solvent stress in Saccharomyces cerevisiae.
  J Biol Chem, 283, 9768-9775.  
18600322 X.Chu, H.He, C.Guo, and B.Sun (2008).
Identification of two novel esterases from a marine metagenomic library derived from South China Sea.
  Appl Microbiol Biotechnol, 80, 615-625.  
17973159 X.Yang, X.Lin, T.Fan, J.Bian, and X.Huang (2008).
Cloning and Expression of lipP, A Gene Encoding a Cold-Adapted Lipase from Moritella sp.2-5-10-1.
  Curr Microbiol, 56, 194-198.  
17625021 J.S.Byun, J.K.Rhee, N.D.Kim, J.Yoon, D.U.Kim, E.Koh, J.W.Oh, and H.S.Cho (2007).
Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties.
  BMC Struct Biol, 7, 47.
PDB code: 2c7b
  17620715 S.Kim, S.Joo, H.C.Yoon, Y.Ryu, K.K.Kim, and T.D.Kim (2007).
Purification, crystallization and preliminary crystallographic analysis of Est25: a ketoprofen-specific hormone-sensitive lipase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 579-581.  
16354661 C.Deb, J.Daniel, T.D.Sirakova, B.Abomoelak, V.S.Dubey, and P.E.Kolattukudy (2006).
A novel lipase belonging to the hormone-sensitive lipase family induced under starvation to utilize stored triacylglycerol in Mycobacterium tuberculosis.
  J Biol Chem, 281, 3866-3875.  
16551354 G.Schneider, G.Neuberger, M.Wildpaner, S.Tian, I.Berezovsky, and F.Eisenhaber (2006).
Application of a sensitive collection heuristic for very large protein families: evolutionary relationship between adipose triglyceride lipase (ATGL) and classic mammalian lipases.
  BMC Bioinformatics, 7, 164.  
16287140 J.Bielnicki, Y.Devedjiev, U.Derewenda, Z.Dauter, A.Joachimiak, and Z.S.Derewenda (2006).
B. subtilis ykuD protein at 2.0 A resolution: insights into the structure and function of a novel, ubiquitous family of bacterial enzymes.
  Proteins, 62, 144-151.
PDB code: 1y7m
16598011 J.K.Rhee, D.Y.Kim, D.G.Ahn, J.H.Yun, S.H.Jang, H.C.Shin, H.S.Cho, J.G.Pan, and J.W.Oh (2006).
Analysis of the thermostability determinants of hyperthermophilic esterase EstE1 based on its predicted three-dimensional structure.
  Appl Environ Microbiol, 72, 3021-3025.  
  16511287 J.S.Byun, J.K.Rhee, D.U.Kim, J.W.Oh, and H.S.Cho (2006).
Crystallization and preliminary X-ray crystallographic analysis of EstE1, a new and thermostable esterase cloned from a metagenomic library.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 145-147.  
15837391 B.M.Nair, L.A.Joachimiak, S.Chattopadhyay, I.Montano, and J.L.Burns (2005).
Conservation of a novel protein associated with an antibiotic efflux operon in Burkholderia cenocepacia.
  FEMS Microbiol Lett, 245, 337-344.  
15691936 J.K.Rhee, D.G.Ahn, Y.G.Kim, and J.W.Oh (2005).
New thermophilic and thermostable esterase with sequence similarity to the hormone-sensitive lipase family, cloned from a metagenomic library.
  Appl Environ Microbiol, 71, 817-825.
PDB code: 2bzq
15613384 J.R.Bradford, and D.R.Westhead (2005).
Improved prediction of protein-protein binding sites using a support vector machines approach.
  Bioinformatics, 21, 1487-1494.  
15624212 J.W.Arndt, R.Schwarzenbacher, R.Page, P.Abdubek, E.Ambing, T.Biorac, J.M.Canaves, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, A.Godzik, C.Grittini, S.K.Grzechnik, J.Hale, E.Hampton, G.W.Han, J.Haugen, M.Hornsby, H.E.Klock, E.Koesema, A.Kreusch, P.Kuhn, L.Jaroszewski, S.A.Lesley, I.Levin, D.McMullan, T.M.McPhillips, M.D.Miller, A.Morse, K.Moy, E.Nigoghossian, J.Ouyang, W.S.Peti, K.Quijano, R.Reyes, E.Sims, G.Spraggon, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, F.von Delft, X.Wang, B.West, A.White, G.Wolf, Q.Xu, O.Zagnitko, K.O.Hodgson, J.Wooley, and I.A.Wilson (2005).
Crystal structure of an alpha/beta serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 1.85 A resolution.
  Proteins, 58, 755-758.
PDB code: 1vkh
14617621 G.De Simone, L.Mandrich, V.Menchise, V.Giordano, F.Febbraio, M.Rossi, C.Pedone, and G.Manco (2004).
A substrate-induced switch in the reaction mechanism of a thermophilic esterase: kinetic evidences and structural basis.
  J Biol Chem, 279, 6815-6823.
PDB code: 1qz3
15373841 S.Canaan, D.Maurin, H.Chahinian, B.Pouilly, C.Durousseau, F.Frassinetti, L.Scappuccini-Calvo, C.Cambillau, and Y.Bourne (2004).
Expression and characterization of the protein Rv1399c from Mycobacterium tuberculosis. A novel carboxyl esterase structurally related to the HSL family.
  Eur J Biochem, 271, 3953-3961.  
15365646 S.W.Lee, K.Won, H.K.Lim, J.C.Kim, G.J.Choi, and K.Y.Cho (2004).
Screening for novel lipolytic enzymes from uncultured soil microorganisms.
  Appl Microbiol Biotechnol, 65, 720-726.  
15184114 Y.J.Choi, C.B.Miguez, and B.H.Lee (2004).
Characterization and heterologous gene expression of a novel esterase from Lactobacillus casei CL96.
  Appl Environ Microbiol, 70, 3213-3221.  
15286736 Y.Shi, and P.Burn (2004).
Lipid metabolic enzymes: emerging drug targets for the treatment of obesity.
  Nat Rev Drug Discov, 3, 695-710.  
12482847 J.Grober, S.Lucas, M.Sörhede-Winzell, I.Zaghini, A.Mairal, J.A.Contreras, P.Besnard, C.Holm, and D.Langin (2003).
Hormone-sensitive lipase is a cholesterol esterase of the intestinal mucosa.
  J Biol Chem, 278, 6510-6515.  
12689620 T.Raclot (2003).
Selective mobilization of fatty acids from adipose tissue triacylglycerols.
  Prog Lipid Res, 42, 257-288.  
12925534 W.J.Shen, S.Patel, V.Natu, R.Hong, J.Wang, S.Azhar, and F.B.Kraemer (2003).
Interaction of hormone-sensitive lipase with steroidogenic acute regulatory protein: facilitation of cholesterol transfer in adrenal.
  J Biol Chem, 278, 43870-43876.  
12421810 X.Zhu, N.A.Larsen, A.Basran, N.C.Bruce, and I.A.Wilson (2003).
Observation of an arsenic adduct in an acetyl esterase crystal structure.
  J Biol Chem, 278, 2008-2014.
PDB codes: 1lzk 1lzl
12402324 A.C.Sehgal, R.Tompson, J.Cavanagh, and R.M.Kelly (2002).
Structural and catalytic response to temperature and cosolvents of carboxylesterase EST1 from the extremely thermoacidophilic archaeon Sulfolobus solfataricus P1.
  Biotechnol Bioeng, 80, 784-793.  
11933065 B.Reva, A.Finkelstein, and S.Topiol (2002).
Threading with chemostructural restrictions method for predicting fold and functionally significant residues: application to dipeptidylpeptidase IV (DPP-IV).
  Proteins, 47, 180-193.  
12147492 Y.Hotta, S.Ezaki, H.Atomi, and T.Imanaka (2002).
Extremely stable and versatile carboxylesterase from a hyperthermophilic archaeon.
  Appl Environ Microbiol, 68, 3925-3931.  
10940339 C.Holm, T.Osterlund, H.Laurell, and J.A.Contreras (2000).
Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.
  Annu Rev Nutr, 20, 365-393.  
10707022 S.D'Auria, P.Herman, J.R.Lakowicz, E.Bertoli, F.Tanfani, M.Rossi, and G.Manco (2000).
The thermophilic esterase from Archaeoglobus fulgidus: structure and conformational dynamics at high temperature.
  Proteins, 38, 351-360.  
10694408 W.J.Shen, S.Patel, R.Hong, and F.B.Kraemer (2000).
Hormone-sensitive lipase functions as an oligomer.
  Biochemistry, 39, 2392-2398.  
11080636 Y.Devedjiev, Z.Dauter, S.R.Kuznetsov, T.L.Jones, and Z.S.Derewenda (2000).
Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A.
  Structure, 8, 1137-1146.
PDB code: 1fj2
10842661 C.Londos, D.L.Brasaemle, C.J.Schultz, D.C.Adler-Wailes, D.M.Levin, A.R.Kimmel, and C.M.Rondinone (1999).
On the control of lipolysis in adipocytes.
  Ann N Y Acad Sci, 892, 155-168.  
10607665 M.Nardini, and B.W.Dijkstra (1999).
Alpha/beta hydrolase fold enzymes: the family keeps growing.
  Curr Opin Struct Biol, 9, 732-737.  
10404588 P.Heikinheimo, A.Goldman, C.Jeffries, and D.L.Ollis (1999).
Of barn owls and bankers: a lush variety of alpha/beta hydrolases.
  Structure, 7, R141-R146.  
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.