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==Properties of the imidazole side chain==
The conjugate acid (protonated form) of the [[imidazole]] [[side chain]] in histidine has a [[Acid dissociation constant|p''K''<sub>a</sub>]] of approximately 6.0. Thus, below a pH of 6, the imidazole ring is mostly [[Protonation|protonated]] (as described by the [[Henderson–Hasselbalch equation]]). The resulting imidazolium ring bears two NH bonds and has a positive charge. The positive charge is equally distributed between both [[nitrogen]]s and can be represented with two equally important [[resonance structure]]s. Sometimes, the symbol '''Hip''' is used for this protonated form instead of the usual His.<ref name=":4" /><ref name=":5">{{Cite web |title=HISTIDINE |url=http://ambermd.org/Questions/HIS.html |access-date=2022-05-12 |website=ambermd.org}}</ref><ref name=":6">{{Cite journal |last1=Dokainish |first1=Hisham M. |last2=Kitao |first2=Akio |date=2016-08-05 |title=Computational Assignment of the Histidine Protonation State in (6-4) Photolyase Enzyme and Its Effect on the Protonation Step |journal=ACS Catalysis |language=en |volume=6 |issue=8 |pages=5500–5507 |doi=10.1021/acscatal.6b01094 |s2cid=88813605 |issn=2155-5435|doi-access=free }}</ref> Above pH 6, one of the two protons is lost. The remaining proton of the imidazole ring can reside on either nitrogen, giving rise to what are known as the N1-H or N3-H [[tautomer]]s. The N3-H tautomer is shown in the figure above. In the N1-H tautomer, the NH is nearer the backbone. These neutral tautomers, also referred to as Nδ and Nε, are sometimes referred to with symbols '''Hid''' and '''Hie''', respectively.<ref name=":4">{{Cite journal |last1=Kim |first1=Meekyum Olivia |last2=Nichols |first2=Sara E. |last3=Wang |first3=Yi |last4=McCammon |first4=J. Andrew |date=March 2013 |title=Effects of histidine protonation and rotameric states on virtual screening of M. tuberculosis RmlC |journal=Journal of Computer-Aided Molecular Design |language=en |volume=27 |issue=3 |pages=235–246 |doi=10.1007/s10822-013-9643-9 |issn=0920-654X |pmc=3639364 |pmid=23579613|bibcode=2013JCAMD..27..235K }}</ref><ref name=":5" /><ref name=":6" /> The imidazole/imidazolium ring of histidine is [[aromatic]] at all pH values.<ref>{{cite journal |doi=10.1016/S0022-2860(03)00282-5 |title=Five-membered heterocycles. Part III. Aromaticity of 1,3-imidazole in 5+n hetero-bicyclic molecules |year=2003 |last1=Mrozek |first1=Agnieszka |last2=Karolak-Wojciechowska |first2=Janina |last3=Kieć-Kononowicz |first3=Katarzyna |journal=Journal of Molecular Structure |volume=655 |issue=3 |pages=397–403 |bibcode=2003JMoSt.655..397M}}</ref> Under certain conditions, all three ion-forming groups of histidine can be charged forming the histidinium cation.<ref>{{Cite journal |
The acid-base properties of the imidazole side chain are relevant to the [[catalyst|catalytic mechanism]] of many [[enzyme]]s.<ref name=":0">{{Cite journal|last=Ingle|first=Robert A.|title=Histidine Biosynthesis|journal=The Arabidopsis Book|volume=9|pages=e0141|doi=10.1199/tab.0141|pmc=3266711|pmid=22303266|year=2011}}</ref> In [[catalytic triad]]s, the basic nitrogen of histidine abstracts a proton from [[serine]], [[threonine]], or [[cysteine]] to activate it as a [[nucleophile]]. In a histidine [[proton shuttle]], histidine is used to quickly shuttle protons. It can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen. In [[carbonic anhydrase]]s, a histidine proton shuttle is utilized to rapidly shuttle protons away from a [[zinc]]-bound water molecule to quickly regenerate the active form of the enzyme. In helices E and F of [[haemoglobin]], histidine influences binding of dioxygen as well as [[carbon monoxide]]. This interaction enhances the affinity of Fe(II) for O2 but destabilizes the binding of CO, which binds only 200 times stronger in haemoglobin, compared to 20,000 times stronger in free [[haem]].
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[[Image:Succinate Dehygrogenase 1YQ3 Haem group.png|thumb|left|The histidine-bound [[heme]] group of [[succinate dehydrogenase]], an [[electron carrier]] in the [[mitochondria]]l [[electron transfer chain]]. The large semi-transparent sphere indicates the location of the [[iron]] [[ion]]. From {{PDB|1YQ3}}.|205x205px]]
[[Image:Cu3Im8laccase.png|thumb|left|The tricopper site found in many [[laccase]]s, notice that each [[copper]] center is bound to the [[imidazole]] sidechains of histidine (color code: copper is brown, [[nitrogen]] is blue).]]
Histidine forms [[amino acid complex|complexes]] with many metal ions. The imidazole sidechain of the histidine residue commonly serves as a [[ligand]] in [[metalloprotein]]s. One example is the axial base attached to Fe in myoglobin and hemoglobin. Poly-histidine tags (of six or more consecutive H residues) are utilized for protein purification by binding to columns with nickel or cobalt, with micromolar affinity.<ref>{{Cite book|last1=Bornhorst|first1=J. A.|last2=Falke|first2=J. J.|
==Metabolism==
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