Editing Proline (section)

==Properties in protein structure==
The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids.  It also affects the rate of peptide bond formation between proline and other amino acids.  When proline is bound as an amide in a peptide bond, its nitrogen is not bound to any hydrogen, meaning it cannot act as a [[hydrogen bond]] donor, but can be a hydrogen bond acceptor.

Peptide bond formation with incoming Pro-tRNA<sup>Pro</sup> in the ribosome is considerably slower than with any other tRNAs, which is a general feature of ''N''-alkylamino acids.<ref>{{cite journal | vauthors = Pavlov MY, Watts RE, Tan Z, Cornish VW, Ehrenberg M, Forster AC | title = Slow peptide bond formation by proline and other ''N''-alkylamino acids in translation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 1 | pages = 50–54 | date = January 2009 | pmid = 19104062 | pmc = 2629218 | doi = 10.1073/pnas.0809211106 | bibcode = 2009PNAS..106...50P | doi-access = free }}.</ref>  Peptide bond formation is also slow between an incoming tRNA and a chain ending in proline; with the creation of proline-proline bonds slowest of all.<ref>{{cite journal | vauthors = Buskirk AR, Green R | title = Biochemistry. Getting past polyproline pauses | journal = Science | volume = 339 | issue = 6115 | pages = 38–39 | date = January 2013 | pmid = 23288527 | pmc = 3955122 | doi = 10.1126/science.1233338 | bibcode = 2013Sci...339...38B }}</ref>

The exceptional conformational rigidity of proline affects the [[secondary structure]] of proteins near a proline residue and may account for proline's higher prevalence in the proteins of [[thermophile|thermophilic]] organisms.  [[Protein secondary structure]] can be described in terms of the [[dihedral angle]]s [[Dihedral angle#Dihedral angles of biological molecules|φ, ψ and ω]] of the protein backbone.  The cyclic structure of proline's side chain locks the angle φ at approximately −65°.<ref>{{cite journal | vauthors = Morris AL, MacArthur MW, Hutchinson EG, Thornton JM | title = Stereochemical quality of protein structure coordinates | journal = Proteins | volume = 12 | issue = 4 | pages = 345–364 | date = April 1992 | pmid = 1579569 | doi = 10.1002/prot.340120407 | s2cid = 940786 }}</ref>

Proline acts as a structural disruptor in the middle of regular [[secondary structure]] elements such as [[alpha helix|alpha helices]] and [[beta sheet]]s; however, proline is commonly found as the first residue of an [[alpha helix]] and also in the edge strands of [[beta sheet]]s.  Proline is also commonly found in [[turn (biochemistry)|turns]] (another kind of secondary structure), and aids in the formation of beta turns.  This may account for the curious fact that proline is usually solvent-exposed, despite having a completely [[aliphatic]] side chain.

Multiple prolines and/or [[hydroxyproline]]s in a row can create a [[polyproline helix]], the predominant [[secondary structure]] in [[collagen]]. The [[hydroxylation]] of proline by [[prolyl hydroxylase]] (or other additions of electron-withdrawing substituents such as [[fluorine]]) increases the conformational stability of [[collagen]] significantly.<ref name="SzpakJAS">{{Cite journal | vauthors = Szpak P  |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis |url=https://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis |journal=[[Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 |bibcode=2011JArSc..38.3358S |url-status=live |archive-url=https://web.archive.org/web/20120118065911/http://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis |archive-date=2012-01-18 }}</ref>  Hence, the hydroxylation of proline is a critical biochemical process for maintaining the [[connective tissue]] of higher organisms.  Severe diseases such as [[scurvy]] can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary [[vitamin C|ascorbate (vitamin C)]] cofactor.