Carboxylesterase

From Proteopedia

(Difference between revisions)

Revision as of 08:22, 23 April 2019

1 Function
2 3D structures of Carboxylesterase

Function

Carboxylesterase (CE) catalyzes the conversion of a wide variety carboxylic esters to alcohol and carboxylate. The catalytic triad of CE involves serine, glutamic acid or aspartic acid and histidine. Human CE1 (hCE1) is involved in drug metabolism and activation. It catalyzes the hydrolysis of heroin and cocaine.
Human carboxylesterase 1 (rhCES1) has been produced in and isolated from whole Trichoplusia ni larvae. The recombinant protein was crystallized and its structure was solved to 2.2 Å resolution (4ab1). The current structure of rhCES1 represents the first published hexagonal crystal form, despite the fact that all other published examples of hCES1 structures consist of a hexamer in the asymmetric unit. found in this space group, while the three twofold axes at z = 1/4 that intersect on this axis complete the . An gave an r.m.s. deviation of 0.42 Å for 522 Cα atoms (2h7c is colored in red and rhCES1 is in green). An r.m.s. value of 0.47 Å (3132 Cα atoms) was obtained for the , indicating that the quaternary structure is essentially identical in these crystal forms isolated from cultured Sf21 cells, supporting the use of this expression system to produce recombinant enzymes for crystallization studies. Regions of the current structure that differ from the previously reported examples of hCES1 include Ser365–Asp374, which has very poor density. In the 2h7c structure . The poorly defined density for this same region in rhCES1 is consistent with the observation that (the loop of one subunit is in red and the loop of the second subunit is in orange). The current results confirm that rhHCES1 isolated from the T. ni system is essentially identical to previous examples of this enzyme isolated from cultured insect cells, validating the use of the whole insect system as a source for recombinant proteins in structure determination studies.^[1]

For the hydrolysis of cocaine by CE see Cocaethylene Synthesis and Pathophysiology.

3D structures of Carboxylesterase

Carboxylesterase 3D structures

References

↑ Greenblatt HM, Otto TC, Kirkpatrick MG, Kovaleva E, Brown S, Buchman G, Cerasoli DM, Sussman JL. Structure of recombinant human carboxylesterase 1 isolated from whole cabbage looper larvae. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Mar 1;68(Pt 3):269-72., Epub 2012 Feb 15. PMID:22442219 doi:10.1107/S1744309112003326

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

Retrieved from "http://52.214.119.220/wiki/index.php/Carboxylesterase"

Category: Topic Page

@@ Line 1: / Line 1: @@
 <StructureSection load='' size='350' side='right' caption='Human carboxylesterase 1 (PDB code [[4ab1]]).' scene='Journal:Acta_Cryst_F:1/Cv/2'>
+__TOC__
+== Function ==
 '''Carboxylesterase''' (CE) catalyzes the conversion of a wide variety carboxylic esters to alcohol and carboxylate.  The catalytic triad of CE involves serine, glutamic acid or aspartic acid and histidine.  Human CE1 (hCE1) is involved in drug metabolism and activation.  It catalyzes the hydrolysis of heroin and cocaine. <br />
 Human carboxylesterase 1 (rhCES1) has been produced in and isolated from whole ''Trichoplusia ni'' larvae. The recombinant protein was crystallized and its structure was solved to 2.2 Å resolution ([[4ab1]]). The current structure of rhCES1 represents the first published hexagonal crystal form, despite the fact that all other published examples of hCES1 structures consist of a hexamer in the asymmetric unit. <scene name='Journal:Acta_Cryst_F:1/Cv/4'>The trimer of subunits sits around one of the threefold axes</scene> found in this space group, while the three twofold axes at z = 1/4 that intersect on this axis complete the <scene name='Journal:Acta_Cryst_F:1/Cv/5'>hexamer</scene>. An <scene name='Journal:Acta_Cryst_F:1/Cv/6'>alignment of the A chain from PDB entry 2h7c with the asymmetric unit reported here</scene> gave an r.m.s. deviation of 0.42 Å for 522 Cα atoms ([[2h7c]] <font color='red'><b>is colored in red</b></font> and <span style="color:lime;background-color:black;font-weight:bold;">rhCES1 is in green</span>). An r.m.s. value of 0.47 Å (3132 Cα atoms) was obtained for the <scene name='Journal:Acta_Cryst_F:1/Cv/7'>entire 2h7c hexamer superposed with the symmetry-generated rhCES1 hexamer</scene>, indicating that the quaternary structure is essentially identical in these crystal forms isolated from cultured Sf21 cells, supporting the use of this expression system to produce recombinant enzymes for crystallization studies.
@@ Line 11: / Line 14: @@
 </StructureSection>
-==3D structures of Carboxylesterase==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-{{#tree:id=OrganizedByTopic|openlevels=0|
-*CE with α,β-hydrolase fold
-**[[1auo]], [[1aur]] – CE – ''Pseudomonas fluorescens''<br />
-**[[3cn7]], [[3cn9]] - CE – ''Pseudomonas aeruginosa''<br />
-**[[1jji]], [[5frd]] – CE – ''Archaeoglobus fulgidus''<br />
-**[[1r1d]], [[2ogs]], [[2ogt]] – GsCE – ''Geobacillus stearothermophilus''<br />
-**[[1u4n]], [[2hm7]] - AaCE (mutant) – ''Alicyclobacillus acidocaldarius''<br />
-**[[2c7b]] – uaCE – uncultured archaeon<br />
-**[[5gmx]] – CE – uncultured bacterium<br />
-**[[2h1i]] – CE – ''Bacillus cereus''<br />
-**[[4ab1]], [[5a7f]] – hCE1 - human<br />
-**[[5a7h]], [[5a7g]] – hCE1 (mutant)<br />
-**[[3wj1]] – SsCE – ''Sulfolobus shibatae''<br />
-**[[4p9n]] – SsCE (mutant)<br />
-**[[3wj2]] – CE – ''Ferroplasma acidiphilum''<br />
-**[[4c87]], [[4c88]], [[4c89]] – CE – ''Lactobacillus plantarum''<br />
-**[[5thm]] – CE 6 – ''Drosophila melanogaster''<br />
-**[[5ugq]], [[5uno]] – MtCE A – ''Mycobacterium tuberculosis''<br />
-**[[5uoh]] – MtCE A (mutant)<br />
-**[[6avv]] – AtCE sober1 – ''Arabidopsis thaliana'' <br />
-**[[6avw]], [[6avx]] – AtCE sober1 (mutant)<br />
-*CE with α,β-hydrolase fold binary complex
-**[[1k4y]] – CE + pyridino-piperidine – rabbit<br />
-**[[1mx5]] – hCE1 + cocaine analog <br />
-**[[1mx9]] – hCE1 + heroin analog<br />
-**[[1mx1]] – hCE1 + tacrine<br />
-**[[1ya8]] – hCE1 + mevastatin<br />
-**[[1yah]] – hCE1 + etyl ester<br />
-**[[1yaj]] – hCE1 + benzil<br />
-**[[2dqy]] – hCE1 + cholate + palmitate<br />
-**[[2dr0]] - hCE1 + taurocholate<br />
-**[[2dqz]] – hCE1 + CoA + homatropine + palmitate<br />
-**[[2h7c]] - hCE1 + CoA<br />
-**[[2hrq]] – hCE1 + soman<br />
-**[[2hrr]]– hCE1 + tabun<br />
-**[[3k9b]] – hCE1 + cyclosarin<br />
-**[[1qz3]] – AaCE (mutant) + hexadecanesulfonate<br />
-**[[1tqh]] – GsCE + propyl acetate<br />
-**[[2o7r]] - AeCE + propyl acetate – ''Actinidia eriantha''<br />
-**[[2o7v]] – AeCE + paraoxon<br />
-**[[2wkw]] – CE + product analog - ''Alcaligenes''<br />
-**[[4ivk]] – uaCE + cephalothin<br />
-*CE with β-lactamase fold
-**[[1ci9]] – BgCE + DFP – ''Burkholderia gladioli''<br />
-**[[1ci8]] – BgCE<br />
-**[[4ivi]] – CE family VIII – bacterium<br />
-*α-esterase 7 CE
-**[[4fnm]], [[4fng]] – CE (mutant) – blowfly<br />
-**[[5a2g]] – CE – ''Hungatella hathewayi''<br />
-**[[2fj0]] – CE – ''Manduca sexta''<br />
-**[[5ikx]], [[5ivh]], [[5ivk]], [[5ivd]], [[5ivi]] – gbfCE – green bottle fly<br />
-**[[5ch3]], [[5ch5]], [[5c8v]] – gbfCE (mutant) <br />
-**[[5tyj]], [[5tyk]], [[5tyl]], [[5tym]], [[5tyn]], [[5tyo]], [[5typ]] – gbfCE (mutant) + inhibitor <br />
-*Other CEs
-**[[4ccw]] – BsCE NP – ''Bacillus subtilis''<br />
-**[[4ccy]] – BsCE YbfK<br />
-**[[6iq7]] – CmCE – ''Croceicoccus marinus''<br />
-**[[6iq8]] – CmCE (mutant) <br />
-}}
 ==References==
 <references/>
 [[Category:Topic Page]]

Carboxylesterase

From Proteopedia

Revision as of 08:22, 23 April 2019

Contents

Function

3D structures of Carboxylesterase

References

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox