Editing Cooperative binding (section)

=== Multimeric enzymes ===
The activity of many [[enzyme]]s is  [[Allosteric regulation|regulated]] by allosteric effectors. Some of these enzymes are multimeric and carry several binding sites for the regulators.

[[Threonine ammonia-lyase|Threonine deaminase]] was one of the first enzymes suggested to behave like hemoglobin<ref name=Changeux1961>{{cite journal | vauthors = Changeux JP | title = The feedback control mechanisms of biosynthetic L-threonine deaminase by L-isoleucine | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 26 | pages = 313–8 | year = 1961 | pmid = 13878122 | doi = 10.1101/SQB.1961.026.01.037 }}</ref> and shown to bind ligands cooperatively.<ref name=Changeux963>{{cite journal | last1 = Changeux | first1 = J.-P. | year = 1963 | title = 'Allosteric Interactions on Biosynthetic L-threonine Deaminase from E. coli K12 | journal = Cold Spring Harb Symp Quant Biol | volume = 28 | pages = 497–504 | doi=10.1101/sqb.1963.028.01.066}}</ref> It was later shown to be a tetrameric protein.<ref name=Gallagher1998>{{cite journal | vauthors = Gallagher DT, Gilliland GL, Xiao G, Zondlo J, Fisher KE, Chinchilla D, Eisenstein E | title = Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase | journal = Structure | volume = 6 | issue = 4 | pages = 465–75 | date = April 1998 | pmid = 9562556 | doi = 10.1016/s0969-2126(98)00048-3 | doi-access = free }}</ref>

Another enzyme that has been suggested early to bind ligands cooperatively is [[aspartate transcarbamoylase|aspartate trans-carbamylase]].<ref name=Gerhart1962>{{cite journal | vauthors = Gerhart JC, Pardee AB | title = The enzymology of control by feedback inhibition | journal = The Journal of Biological Chemistry | volume = 237 | pages = 891–6 | date = March 1962 | issue = 3 | doi = 10.1016/S0021-9258(18)60389-8 | pmid = 13897943 | doi-access = free }}</ref> Although initial models were consistent with four binding sites,<ref name="Changeux1968">{{cite journal | vauthors = Changeux JP, Rubin MM | title = Allosteric interactions in aspartate transcarbamylase. 3. Interpretation of experimental data in terms of the model of Monod, Wyman, and Changeux | journal = Biochemistry | volume = 7 | issue = 2 | pages = 553–61 | date = February 1968 | pmid = 4868541 | doi = 10.1021/bi00842a601 }}</ref> its structure was later shown to be hexameric by [[William Lipscomb]] and colleagues.<ref name=Honzatko1982>{{cite journal | vauthors = Honzatko RB, Crawford JL, Monaco HL, Ladner JE, Ewards BF, Evans DR, Warren SG, Wiley DC, Ladner RC, Lipscomb WN | title = Crystal and molecular structures of native and CTP-liganded aspartate carbamoyltransferase from Escherichia coli | journal = Journal of Molecular Biology | volume = 160 | issue = 2 | pages = 219–63 | date = September 1982 | pmid = 6757446 | doi = 10.1016/0022-2836(82)90175-9 }}</ref>