View source for Polyneuridine-aldehyde esterase

{{infobox enzyme
| Name       = polyneuridine-aldehyde esterase
| EC_number  = 3.1.1.78
| CAS_number = 87041-55-2
| GO_code    = 0050529
| image      = File:Enzyme Polyneuridine Aldehyde Esterase.png
| width      =
| caption    = Polyneuridine-Aldehyde Esterase 3D Rendering 
}}
The enzyme '''polyneuridine-aldehyde esterase''' (EC 3.1.1.78) [[catalysis|catalyzes]] the following reaction:<ref name="Pfitzner_Stöckigt_1983">{{cite journal |vauthors=Pfitzner A, Stöckigt J | title = Characterization of polyneuridine aldehyde esterase, a key enzyme in the biosynthesis of sarpagine/ajmaline type alkaloids | journal = Planta Med. | volume = 48 | issue = 8 | pages = 221–7 |date=August 1983 | pmid = 17404987 | doi = 10.1055/s-2007-969924 }}</ref>

:polyneuridine aldehyde + H<sub>2</sub>O <math>\rightleftharpoons</math> 16-epivellosimine + CO<sub>2</sub> + methanol

This enzyme participates in indole alkaloid biosynthesis.

== Nomenclature ==

This enzyme belongs to the family of [[hydrolase]]s, specifically those acting on carboxylic [[ester]] bonds.  The [[List of enzymes|systematic name]] is '''polyneuridine aldehyde hydrolase (decarboxylating)'''. Other names in common use include:
* polyneuridine aldehyde esterase 
* PNAE

== Homologues ==
This enzyme is found in various forms in plant species such as ''[[Arabidopsis thaliana]]'', ''[[Glycine max]]'' (soybean), ''[[Vitis vinifera]]'' (wine grape), and ''[[Solanum lycopersicum]]'' (tomato) among others.

Polyneuridine-aldehyde esterase also appears in select bacteria including ''[[Enterobacter cloacae]]''.

== Structure ==
The secondary structure of this enzyme consists mainly of [[alpha helices|α helices]]. In its native form, this enzyme has a tertiary structure that includes two main lobes (as depicted above in the blue 3D representation on the top right).

== Reaction ==

{|
|[[File:Polyneuridine aldehyde.png|150px|frameless]]
|<math>\xrightarrow[+ H_2O\ -CH_3OH]{polyneuridine-aldehyde\ esterase}</math>
|[[File:Polyneuridine beta-aldehydoacid.png|150px|frameless]]
|<math>\xrightarrow[- CO_2]{}</math>
|[[File:16-Epivellosimine.png|150px|frameless]]
|}

Polyneuridine-aldehyde esterase catalyzes the [[hydrolysis]] of the [[methyl]] [[ester]] in polyneuridine aldehyde to form polyneuridine β-aldehydoacid and methanol. The [[carboxylic acid]] in the product spontaneously undergoes [[decarboxylation]], yielding 16-epivellosimine and carbon dioxide.<ref name="Pfitzner_Stöckigt_1983"/>

== Mechanism ==
[[File:3GZJ.png|thumb|[[X-ray crystallography#Biological macromolecular crystallography|Crystallographic structure]] of polyneuridine aldehyde esterase from ''[[Rauvolfia serpentina]]'' (rainbow colored, [[N-terminus]] = blue, [[C-terminus]] = red).  The enzyme is complexed with its [[product (biology)|product]] 16-epi-vellosimine that is depicted as a [[space-filling model]] (carbon = white, oxygen = red, nitrogen = blue).<ref name="pmid19496101">{{PDB|3GZJ}}; {{cite journal |vauthors=Yang L, Hill M, Wang M, Panjikar S, Stöckigt J | title = Structural basis and enzymatic mechanism of the biosynthesis of C9- from C10-monoterpenoid indole alkaloids | journal = Angew. Chem. Int. Ed. Engl. | volume = 48 | issue = 28 | pages = 5211–3 | year = 2009 | pmid = 19496101 | doi = 10.1002/anie.200900150 | url = http://bib-pubdb1.desy.de/record/92151 }}</ref>]]

The mechanism of hydrolysis performed by polyneuridine-aldehyde esterase is not known. It has been suggested that the enzyme utilizes a [[catalytic triad]] composed of Ser-87, Asp-216 and His-244.<ref name="Mattern-Dogru_2002">{{cite journal |vauthors=Mattern-Dogru E, Ma X, Hartmann J, Decker H, Stöckigt J | title = Potential active-site residues in polyneuridine aldehyde esterase, a central enzyme of indole alkaloid biosynthesis, by modelling and site-directed mutagenesis | journal = Eur. J. Biochem. | volume = 269 | issue = 12 | pages = 2889–96 |date=June 2002 | pmid = 12071952 | doi = 10.1046/j.1432-1033.2002.02956.x | doi-access = free }}</ref> The catalytic amino acid order is the same as the order of enzymes that are part of the [[alpha/beta hydrolase fold|α/β hydrolase]] family. Thus polyneuridine-aldehyde esterase may be a novel member of the α/β hydrolase group.<ref name="Dogru">{{cite journal |vauthors=Dogru E, Warzecha H, Seibel F, Haebel S, Lottspeich F, Stöckigt J | title = The gene encoding polyneuridine aldehyde esterase of monoterpenoid indole alkaloid biosynthesis in plants is an ortholog of the alpha/betahydrolase super family | journal = Eur. J. Biochem. | volume = 267 | issue = 5 | pages = 1397–406 |date=March 2000 | pmid = 10691977 | doi = 10.1046/j.1432-1327.2000.01136.x | doi-access =  }}</ref>

==Broader significance==
This enzyme is a part of the pathway of [[indole alkaloid]] biosynthesis. The indole alkaloids that result from this metabolic pathway are used by many plant species as a defense against herbivores and parasites.

== Open questions ==
The precise mechanisms by which this enzyme performs its function is still unknown. As noted above, researchers are formulating suggestions as to how polyneuridine-aldehyde esterase catalyses the decomposition of polyneuridine-aldehyde, but a mechanism has not yet been affirmed with absolute certainty. Due to the lack of complete understanding of polyneuridine-aldehyde esterase's precise mechanism, this enzyme cannot be grouped into a family of enzymes. Based on mechanism theories, suggestions can be made as to how this enzyme should be categorized, and some parallels can be drawn between polyneuridine-aldehyde esterase and other enzymes.

==References==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal |vauthors=Pfitzner A, Stockigt J| year = 1983 | title = Polyneuridine aldehyde esterase: an unusual specific enzyme involved in the biosynthesis of sarpagine type alkaloids | journal = Journal of the Chemical Society, Chemical Communications | issue = 8 | pages = 459&ndash;460 | doi = 10.1039/C39830000459 }}
{{refend}}

{{Esterases}}
{{Enzymes}}
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[[Category:EC 3.1.1]]
[[Category:Enzymes of unknown structure]]