View source for Enolase

{{Use dmy dates|date=January 2014}}

{{enzyme
| Name = phosphopyruvate hydratase
| EC_number = 4.2.1.11
| CAS_number = 9014-08-8
| IUBMB_EC_number = 4/2/1/11
| GO_code = 0004634
| image = Enolase 2ONE wpmp.png
| width = 
| caption = Yeast enolase dimer.<ref name="pmid9376357">{{PDB|2ONE}}; {{cite journal | vauthors = Zhang E, Brewer JM, Minor W, Carreira LA, Lebioda L | title = Mechanism of enolase: the crystal structure of asymmetric dimer enolase-2-phospho-D-glycerate/enolase-phosphoenolpyruvate at 2.0 A resolution | journal = Biochemistry | volume = 36 | issue = 41 | pages = 12526–34 | date = October 1997 | pmid = 9376357 | doi = 10.1021/bi9712450 }}</ref>
}}
{{Infobox protein family
| Symbol = Enolase_N
| Name = Enolase, N-terminal domain
| image = PDB 1pdz EBI.jpg
| width = 
| caption = x-ray structure and catalytic mechanism of lobster enolase
| Pfam = PF03952
| Pfam_clan = CL0227 
| InterPro = IPR020811
| SMART = 
| PROSITE = PDOC00148
| MEROPS = 
| SCOP = 1els
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{Pfam box 
| Symbol = Enolase 
| Name = Enolase 
| Pfam = PF00113 
| InterPro = IPR000941 
| PROSITE = PDOC00148 
| PDB = {{PDB|1e9i}} {{PDB|1ebg}} {{PDB|1ebh}} {{PDB|1els}} {{PDB|1iyx}} {{PDB|1l8p}} {{PDB|1nel}} {{PDB|1oep}} {{PDB|1one}} {{PDB|1p43}} 
| image = 2XSX.pdb.png
| width = 
| caption = Crystal structure of dimeric beta human enolase [[ENO3]].<ref name="Vollmar_2010">{{PDB|2XSX}}; {{cite journal |vauthors=Vollmar M, Krysztofinska E, Chaikuad A, Krojer T, Cocking R, Vondelft F, Bountra C, Arrowsmith CH, Weigelt J, Edwards A, Yue WW, Oppermann U |title = Crystal structure of human beta enolase ENOB | journal = To be Published | year = 2010}}</ref>
}}

'''Enolase''', also known as '''phosphopyruvate hydratase''', is a [[metalloenzyme]] responsible for the catalysis of the conversion of [[2-phosphoglycerate]] (2-PG) to [[phosphoenolpyruvate]] (PEP), the ninth and penultimate step of [[glycolysis]]. The [[chemical reaction]] catalyzed by enolase is:

:2-phospho-D-glycerate <math>\rightleftharpoons</math> phosphoenolpyruvate + H<sub>2</sub>O

Enolase belongs to the family of [[lyase]]s, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this [[enzyme]] is '''2-phospho-D-glycerate hydro-lyase (phosphoenolpyruvate-forming)'''.

The reaction is reversible, depending on environmental concentrations of substrates.<ref name=Pancholi>{{cite journal | vauthors = Pancholi V | title = Multifunctional alpha-enolase: its role in diseases | journal = Cellular and Molecular Life Sciences | volume = 58 | issue = 7 | pages = 902–20 | date = June 2001 | pmid = 11497239 | doi = 10.1007/PL00000910 | url = http://link.springer.de/link/service/journals/00018/bibs/1058007/10580902.htm | archive-url = https://archive.today/20130105234536/http://link.springer.de/link/service/journals/00018/bibs/1058007/10580902.htm | url-status = dead | archive-date = 2013-01-05 }}</ref> The optimum pH for the human enzyme is 6.5.<ref name=Hoorn>{{cite journal |vauthors=Hoorn RK, Flickweert JP, Staal GE |title=Purification and properties of enolase of human erythroctyes |journal=Int J Biochem |volume=5 |issue= 11–12|pages=845–52 |year=1974 |doi=10.1016/0020-711X(74)90119-0|hdl=1874/18158 |hdl-access=free }}</ref> Enolase is present in all tissues and organisms capable of glycolysis or [[fermentation (biochemistry)|fermentation]]. The enzyme was discovered by Lohmann and [[Otto Fritz Meyerhof|Meyerhof]] in 1934,<!--

--><ref name="Lohmann_Meyerhof_1934">Lohman K & Meyerhof O (1934) Über die enzymatische umwandlung von phosphoglyzerinsäure in brenztraubensäure und phosphorsäure (Enzymatic transformation of phosphoglyceric acid into pyruvic and phosphoric acid). Biochem Z 273, 60–72.</ref><!--

--><nowiki> </nowiki>and has since been isolated from a variety of sources including human muscle and [[erythrocytes]].<ref name=Hoorn/> In humans, [[Enolase deficiency|deficiency of ENO1]] is linked to hereditary [[haemolytic anemia]], while ENO3 deficiency is linked to [[glycogen storage disease]] [[Glycogen storage disease type X|type X]].

== Isozymes ==

In humans there are three subunits of enolase, [[alpha-enolase|α]], [[ENO3|β]], and [[ENO2|γ]], each encoded by a separate gene that can combine to form five different [[isoenzymes]]: αα, αβ, αγ, ββ, and γγ.<ref name=Pancholi/><ref name=Peshavaria>{{cite journal | vauthors = Peshavaria M, Day IN | title = Molecular structure of the human muscle-specific enolase gene (ENO3) | journal = The Biochemical Journal | volume = 275 | issue = Pt 2 | pages = 427–33 | date = April 1991 | pmid = 1840492 | pmc = 1150071 | doi = 10.1042/bj2750427 }}</ref> Three of these isoenzymes (all homodimers) are more commonly found in adult human cells than the others:

* αα or non-neuronal enolase (NNE). Also known as [[alpha-enolase|enolase 1]]. Found in a variety of tissues, including liver, brain, kidney, spleen, adipose. It is present at some level in all normal human cells.
* ββ or muscle-specific enolase (MSE). Also known as [[ENO3|enolase 3]]. This enzyme is largely restricted to muscle where it is present at very high levels in muscle.
* γγ or neuron-specific enolase (NSE). Also known as [[enolase 2]]. Expressed at very high levels in neurons and neural tissues, where it can account for as much as 3% of total soluble protein. It is expressed at much lower levels in most mammalian cells.

When present in the same cell, different isozymes readily form heterodimers.{{Citation needed|reason=What research article states this?|date=July 2017}}

== Structure ==
Enolase is a member of the large [[enolase superfamily]]. It has a molecular weight of 82,000-100,000 Daltons depending on the isoform.<ref name=Pancholi/><ref name=Hoorn/> In human [[alpha enolase]], the two subunits are [[Antiparallel (biochemistry)|antiparallel]] in orientation so that [[Glutamate|Glu]]<sup>20</sup> of one subunit forms an ionic bond with [[Arginine|Arg]]<sup>414</sup> of the other subunit.<ref name=Pancholi/> Each subunit has two distinct domains. The smaller N-terminal domain consists of three [[Alpha helix|α-helices]] and four [[Beta sheet|β-sheets]].<ref name=Pancholi/><ref name=Peshavaria/> The larger C-terminal domain starts with two β-sheets followed by two α-helices and ends with a barrel composed of alternating β-sheets and α-helices arranged so that the β-beta sheets are surrounded by the α-helices.<ref name=Pancholi/><ref name=Peshavaria/> The enzyme's compact, globular structure results from significant hydrophobic interactions between these two domains.

Enolase is a highly conserved enzyme with five active-site residues being especially important for activity. When compared to wild-type enolase, a mutant enolase that differs at either the Glu<sup>168</sup>, Glu<sup>211</sup>, [[Lysine|Lys]]<sup>345</sup>, or Lys<sup>396</sup> residue has an activity level that is cut by a factor of 105.<ref name=Pancholi/> Also, changes affecting [[Histidine|His]]<sup>159</sup> leave the mutant with only 0.01% of its catalytic activity.<ref name=Pancholi/> An integral part of enolase are two Mg<sup>2+</sup> cofactors in the active site, which serve to stabilize negative charges in the substrate.<ref name=Pancholi/><ref name=Peshavaria/>

Recently, moonlighting functions of several enolases, such as interaction with plasminogen, have brought interest to the enzymes' catalytic loops and their structural diversity.<ref>{{cite journal | vauthors = Ehinger S, Schubert WD, Bergmann S, Hammerschmidt S, Heinz DW | title = Plasmin(ogen)-binding alpha-enolase from Streptococcus pneumoniae: crystal structure and evaluation of plasmin(ogen)-binding sites | journal = Journal of Molecular Biology | volume = 343 | issue = 4 | pages = 997–1005 | date = October 2004 | pmid = 15476816 | doi = 10.1016/j.jmb.2004.08.088 }}</ref><ref>{{cite journal | vauthors = Raghunathan K, Harris PT, Spurbeck RR, Arvidson CG, Arvidson DN | title = Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase from Lactobacillus gasseri | journal = FEBS Letters | volume = 588 | issue = 14 | pages = 2212–6 | date = June 2014 | pmid = 24859038 | doi = 10.1016/j.febslet.2014.05.020 }}</ref>

{{Gallery
|title=
|width=350
|height=220
|lines=4
| Image:Enolase with differentiated subunits.jpg|3-D depiction of enolase dimer in antiparallel orientation. One dimer’s N-terminal Glu<sup>20</sup> forms an ionic bond with the other’s C-terminal Arg<sup>414</sup> to stabilize the enzyme’s quaternary structure.
<!-- Image with unknown copyright status removed: Image:Enolase domains & ribbon structure.png|Depiction of one enolase subunit. 3-D surface of C-terminal (yellow) and N-terminal (purple) domains is superimposed on secondary ribbon structure of enolase. -->
|Image:Enolase active site.jpg|Active site of enolase in the middle of the C-terminal domain’s barrel. Depicted are two Mg<sup>2+</sup> cofactors and five highly conserved residues imperative for proper catalytic function: His<sup>159</sup>, Glu<sup>168</sup>, Glu<sup>211</sup>, Lys<sup>345</sup>, Lys<sup>396</sup>.
}}

== Mechanism ==
[[Image:Enolase mechanism2.png|thumb|500px|Mechanism for conversion of 2PG to PEP.]]
Using isotopic probes, the overall mechanism for converting 2-PG to PEP is proposed to be an [[E1cb|E1cB elimination reaction]] involving a carbanion intermediate.<ref>{{cite journal |vauthors=Dinovo EC, Boyer PD |title=Isotopic probes of the enolase reaction mechanism |journal=J Biol Chem |volume=240 |issue= |pages=4586–93 |year=1971}}</ref> The following detailed mechanism is based on studies of crystal structure and [[Chemical kinetics|kinetics]].<ref name=Pancholi/><ref>{{cite journal | vauthors = Poyner RR, Laughlin LT, Sowa GA, Reed GH | title = Toward identification of acid/base catalysts in the active site of enolase: comparison of the properties of K345A, E168Q, and E211Q variants | journal = Biochemistry | volume = 35 | issue = 5 | pages = 1692–9 | date = February 1996 | pmid = 8634301 | doi = 10.1021/bi952186y }}</ref><ref>{{cite journal | vauthors = Reed GH, Poyner RR, Larsen TM, Wedekind JE, Rayment I | title = Structural and mechanistic studies of enolase | journal = Current Opinion in Structural Biology | volume = 6 | issue = 6 | pages = 736–43 | date = December 1996 | pmid = 8994873 | doi = 10.1016/S0959-440X(96)80002-9 }}</ref><ref>{{cite journal | vauthors = Wedekind JE, Reed GH, Rayment I | title = Octahedral coordination at the high-affinity metal site in enolase: crystallographic analysis of the MgII--enzyme complex from yeast at 1.9 A resolution | journal = Biochemistry | volume = 34 | issue = 13 | pages = 4325–30 | date = April 1995 | pmid = 7703246 | doi = 10.1021/bi00013a022 }}</ref><ref>{{cite journal | vauthors = Wedekind JE, Poyner RR, Reed GH, Rayment I | title = Chelation of serine 39 to Mg2+ latches a gate at the active site of enolase: structure of the bis(Mg2+) complex of yeast enolase and the intermediate analog phosphonoacetohydroxamate at 2.1-A resolution | journal = Biochemistry | volume = 33 | issue = 31 | pages = 9333–42 | date = August 1994 | pmid = 8049235 | doi = 10.1021/bi00197a038 }}</ref><ref>{{cite journal | vauthors = Larsen TM, Wedekind JE, Rayment I, Reed GH | title = A carboxylate oxygen of the substrate bridges the magnesium ions at the active site of enolase: structure of the yeast enzyme complexed with the equilibrium mixture of 2-phosphoglycerate and phosphoenolpyruvate at 1.8 A resolution | journal = Biochemistry | volume = 35 | issue = 14 | pages = 4349–58 | date = April 1996 | pmid = 8605183 | doi = 10.1021/bi952859c }}</ref><ref>{{cite journal | vauthors = Duquerroy S, Camus C, Janin J | title = X-ray structure and catalytic mechanism of lobster enolase | journal = Biochemistry | volume = 34 | issue = 39 | pages = 12513–23 | date = October 1995 | pmid = 7547999 | doi = 10.1021/bi00039a005 }}</ref> When the substrate, 2-phosphoglycerate, binds to α-enolase, its carboxyl group coordinates with two magnesium ion cofactors in the active site. This stabilizes the negative charge on the deprotonated oxygen while increasing the acidity of the alpha hydrogen. Enolase's Lys<sup>345</sup> deprotonates the alpha hydrogen, and the resulting negative charge is stabilized by resonance to the carboxylate oxygen and by the magnesium ion cofactors. Following the creation of the carbanion intermediate, the hydroxide on C3 is eliminated as water with the help of Glu<sup>211</sup>, and PEP is formed.

Additionally, conformational changes occur within the enzyme that aid catalysis. In human α-enolase, the substrate is rotated into position upon binding to the enzyme due to interactions with the two catalytic magnesium ions, [[Glutamine|Gln]]<sup>167</sup>, and Lys<sup>396</sup>. Movements of loops [[Serine|Ser]]<sup>36</sup> to His<sup>43</sup>, Ser<sup>158</sup> to [[Glycine|Gly]]<sup>162</sup>, and [[Aspartate|Asp]]<sup>255</sup> to [[Asparagine|Asn]]<sup>256</sup> allow Ser<sup>39</sup> to coordinate with Mg<sup>2+</sup> and close off the active site. In addition to coordination with the catalytic magnesium ions, the pKa of the substrate's alpha hydrogen is also lowered due to protonation of the phosphoryl group by His<sup>159</sup> and its proximity to Arg<sup>374</sup>. Arg<sup>374</sup> also causes Lys<sup>345</sup> in the active site to become deprotonated, which primes Lys<sup>345</sup> for its role in the mechanism.

== Diagnostic uses ==
In recent medical experiments, enolase concentrations have been sampled in an attempt to diagnose certain conditions and their severity. For example, higher concentrations of enolase in [[cerebrospinal fluid]] more strongly correlated to low-grade [[astrocytoma]] than did other enzymes tested ([[aldolase]], [[pyruvate kinase]], [[creatine kinase]], and [[lactate dehydrogenase]]).<ref>{{cite journal | vauthors = Royds JA, Timperley WR, Taylor CB | title = Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 44 | issue = 12 | pages = 1129–35 | date = December 1981 | pmid = 7334408 | pmc = 491233 | doi = 10.1136/jnnp.44.12.1129 }}</ref> The same study showed that the fastest rate of tumor growth occurred in patients with the highest levels of CSF enolase.
Increased levels of enolase have also been identified in patients who have suffered a recent [[myocardial infarction]] or [[cerebrovascular accident]]. It has been inferred that levels of CSF neuron-specific enolase, [[Blood plasma|serum]] NSE, and creatine kinase (type BB) are indicative in the prognostic assessment of cardiac arrest victims.<ref>{{cite journal | vauthors = Roine RO, Somer H, Kaste M, Viinikka L, Karonen SL | title = Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis | journal = Archives of Neurology | volume = 46 | issue = 7 | pages = 753–6 | date = July 1989 | pmid = 2742544 | doi = 10.1001/archneur.1989.00520430047015 }}</ref> Other studies have focused on the prognostic value of NSE values in cerebrovascular accident victims.<ref>{{cite journal | vauthors = Hay E, Royds JA, Davies-Jones GA, Lewtas NA, Timperley WR, Taylor CB | title = Cerebrospinal fluid enolase in stroke | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 47 | issue = 7 | pages = 724–9 | date = July 1984 | pmid = 6747647 | pmc = 1027902 | doi = 10.1136/jnnp.47.7.724 }}</ref>

[[Autoantibodies]] to alpha-enolase are associated with the rare syndrome called [[Hashimoto's encephalopathy]].<ref name="pmid15833368">{{cite journal | vauthors = Fujii A, Yoneda M, Ito T, Yamamura O, Satomi S, Higa H, Kimura A, Suzuki M, Yamashita M, Yuasa T, Suzuki H, Kuriyama M | title = Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy | journal = Journal of Neuroimmunology | volume = 162 | issue = 1–2 | pages = 130–6 | date = May 2005 | pmid = 15833368 | doi = 10.1016/j.jneuroim.2005.02.004 }}</ref>

== Inhibitors ==
Small-molecule inhibitors of enolase have been synthesized as chemical probes (substrate-analogues) of the catalytic mechanism of the enzyme and more recently, have been investigated as potential treatments for cancer and infectious diseases.<ref name="Anderson_1984">{{cite journal | vauthors = Anderson VE, Weiss PM, Cleland WW | title = Reaction intermediate analogues for enolase | journal = Biochemistry | volume = 23 | issue = 12 | pages = 2779–86 | date = June 1984 | pmid = 6380574 | doi=10.1021/bi00307a038}}</ref><ref name="Jung_2013">{{cite journal | authors = Jung DW, Kim WH, Park SH, Lee J, Kim J, Su D, Ha HH, Chang YT, Williams DR.  | title = A unique small molecule inhibitor of enolase clarifies its role in fundamental biological processes. | journal = ACS Chemical Biology | volume = 8 | issue = 6 | pages = 1271–1282 | date = April 2, 2013 | pmid = 23547795 | doi = 10.1021/cb300687k}}</ref> Most inhibitors have metal chelating properties and bind to enzyme by interactions with the structural Magnesium Atom Mg(A).<ref name="Poyner_1992">{{cite journal | vauthors = Poyner RR, Reed GH | title = Structure of the bis divalent cation complex with phosphonoacetohydroxamate at the active site of enolase | journal = Biochemistry | volume = 31 | issue = 31 | pages = 7166–73 | date = August 1992 | pmid = 1322695 | doi=10.1021/bi00146a020}}</ref><ref name="Zhang_1994">{{cite journal | vauthors = Zhang E, Hatada M, Brewer JM, Lebioda L | title = Catalytic metal ion binding in enolase: the crystal structure of an enolase-Mn2+-phosphonoacetohydroxamate complex at 2.4-A resolution | journal = Biochemistry | volume = 33 | issue = 20 | pages = 6295–300 | date = May 1994 | pmid = 8193144 | doi=10.1021/bi00186a032}}</ref> The most potent of these is phosphonoacetohydroxamate,<ref name="Zhang_1994"/> which in its unprotonated form has pM affinity for the enzyme. It has structural similarity to the presumed catalytic intermediate, between PEP and 2-PG. Attempts have been made to use this inhibitor as an anti-trypanosome drug,<ref name="Navarro_2007">{{cite journal | authors = de A S Navarro MV, Gomes Dias SM, Mello LV, da Silva Giotto MT, Gavalda S, Blonski C, Garratt RC, Rigden DJ | title = Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics | journal = The FEBS Journal | volume = 274 | issue = 19 | pages = 5077–89 | date = October 2007 | pmid = 17822439 | doi = 10.1111/j.1742-4658.2007.06027.x | doi-access = free }}</ref> and more recently, as an anti-cancer agent, specifically, in [[glioblastoma]] that are enolase-deficient due to homozygous deletion of the [[ENO1]] gene as part of the 1p36 tumor suppressor locus ([[synthetic lethality]]).<ref name="Muller_2012">{{cite journal | vauthors = Muller FL, Colla S, Aquilanti E, Manzo VE, Genovese G, Lee J, Eisenson D, Narurkar R, Deng P, Nezi L, Lee MA, Hu B, Hu J, Sahin E, Ong D, Fletcher-Sananikone E, Ho D, Kwong L, Brennan C, Wang YA, Chin L, DePinho RA | title = Passenger deletions generate therapeutic vulnerabilities in cancer | journal = Nature | volume = 488 | issue = 7411 | pages = 337–42 | date = August 2012 | pmid = 22895339 | doi = 10.1038/nature11331 | pmc=3712624}}</ref> A natural product [[phosphonate]] antibiotic, SF2312 ([[CAS Registry Number|CAS]] 107729-45-3), which is active against gram positive and negative bacteria especially under anaerobic conditions,<ref name="Watanabe_1986">{{cite journal | authors = Watanabe H, Yoshida J, Tanaka E, Ito M, Miyadoh S, Shomura T. | title = Studies on a new phosphonic acid antibiotic, SF-2312. | journal = Sci Rep Meiji Seika Kaisha.| volume = 25 | pages = 12–17| date = 1986 }}</ref> is a high potency inhibitor of Enolase {{PDB link|4zcw}} that binds in manner similar to phoshphonoacetohydroxamate {{PDB link|4za0}}.<ref name="Leonard_2016">{{cite journal | vauthors = Leonard PG, Satani N, Maxwell D, Lin YH, Hammoudi N, Peng Z, Pisaneschi F, Link TM, Lee GR, Sun D, Prasad BA, Di Francesco ME, Czako B, Asara JM, Wang YA, Bornmann W, DePinho RA, Muller FL | title = SF2312 is a natural phosphonate inhibitor of enolase | journal = Nature Chemical Biology | volume = 12 | issue = 12 | pages = 1053–1058 | date = December 2016 | pmid = 27723749 | doi = 10.1038/nchembio.2195 | pmc=5110371}}</ref> An allosteric binder, ENOblock <ref name="Jung_2013"/> was initially described as an inhibitor of Enolase, but subsequently shown not to actually inhibit the enzyme, but rather, interfere with the Enolase in vitro enzymatic assay. <ref name="Satani N_2016">{{cite journal | authors = Satani N, Lin YH, Hammoudi N, Raghavan S, Georgiou DK, Muller FL.| title =ENOblock Does Not Inhibit the Activity of the Glycolytic Enzyme Enolase.| journal = PLOS ONE | volume = 11 | issue =12| date = December 28, 2016 | pmid = 28030597 | doi = 10.1371/journal.pone.0168739 | pmc=5193436 | page=e0168739}}</ref> ENOblock was found to alter the cellular localization of enolase, influencing its secondary, non-glycolytic functions, such as transcription regulation.<ref name="Cho H_2017">{{cite journal | authors = Cho H, Um J, Lee JH, Kim WH, Kang WS, Kim SH, Ha HH, Kim YC, Ahn YK, Jung DW, Williams DR.| title =ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes.| journal = Scientific Reports | volume = 7 | date = March 8, 2017 | pmid = 28272459 | doi = 10.1038/srep44186 | pmc=5341156 | page=44186}}</ref> Subsequent analysis using a commercial assay also indicated that ENOblock can inhibit enolase activity in biological contexts, such as cells and animal tissues.<ref name="Cho H_2017">{{cite journal | authors = Cho H, Um J, Lee JH, Kim WH, Kang WS, Kim SH, Ha HH, Kim YC, Ahn YK, Jung DW, Williams DR.| title =ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes.| journal = Scientific Reports | volume = 7 | date = March 8, 2017 | pmid = 28272459 | doi = 10.1038/srep44186 | pmc=5341156 | page=44186}}</ref> Methylglyoxal has also been described as an inhibitor of human enolase. <ref name="Pietkiewicz J_2009">{{cite journal | authors = Pietkiewicz J, Gamian A, Staniszewska M, Danielewicz R.| title =Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products.| journal = J Enzyme Inhib Med Chem | volume = 24 | issue = 2 | pages = 356–364 | date = April 29, 2009 | pmid = 18830874 | doi = 10.1080/14756360802187679}}</ref>

[[Fluoride]] is a known competitor of enolase's substrate 2-PG. Fluoride can a complex with magnesium and phosphate, which binds in the active site instead of 2-PG.<ref name="Hoorn" /> One study found that fluoride could inhibit bacterial enolase ''in vitro''<ref>{{cite journal | vauthors = Hüther FJ, Psarros N, Duschner H | title = Isolation, characterization, and inhibition kinetics of enolase from Streptococcus rattus FA-1 | journal = Infection and Immunity | volume = 58 | issue = 4 | pages = 1043–7 | date = April 1990 | pmid = 2318530 | pmc = 258580 | url = http://iai.asm.org/cgi/pmidlookup?view=long&pmid=2318530 }}</ref>

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin}}

* {{cite journal | vauthors = Holt A, Wold F | title = The isolation and characterization of rabbit muscle enolase | journal = The Journal of Biological Chemistry | volume = 236 | pages = 3227–31 | date = December 1961 | pmid = 13908561 }}
* Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 5, Academic Press, New York, 1961, p.&nbsp;471-494.
* {{cite journal | vauthors = Westhead EW, Mclain G | title = A purification of brewers' and bakers' yeast enolase yielding a single active component | journal = The Journal of Biological Chemistry | volume = 239 | pages = 2464–8 | date = August 1964 | pmid = 14235523 }}
{{refend}}

== External links ==
* {{MeshName|Enolase}}

{{glycolysis}}
{{Glycolysis enzymes}}
{{Carbon-oxygen lyases}}

[[Category:Moonlighting proteins]]
<noinclude>

<small>This page was moved from [[:en:Enolase]]. Its edit history can be viewed at [[Enolase/edithistory]]</small></noinclude>