oxyanion hole

{{Short description|Pocket in the active site of an enzyme}}

File:Serine protease oxyanion hole.png (black) stabilises negative charge build-up on the transition state of the substrate (red) using hydrogen bonds from enzyme's backbone amides (blue).]]

An oxyanion hole is a pocket in the active site of an enzyme that stabilizes transition state negative charge on a deprotonated oxygen or alkoxide.{{cite book |vauthors=Stryer L, Berg JM, Tymoczko JL |title = Biochemistry|publisher = W.H. Freeman|location = San Francisco|year = 2002|edition = 5th|isbn = 978-0-7167-4955-4|url = https://www.ncbi.nlm.nih.gov/books/NBK21154/|chapter = 9 Catalytic Strategies|chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK22526/}} The pocket typically consists of backbone amides or positively charged residues. Stabilising the transition state lowers the activation energy necessary for the reaction, and so promotes catalysis.{{Cite journal|title = Enzyme Catalysis by Hydrogen Bonds: The Balance between Transition State Binding and Substrate Binding in Oxyanion Holes|journal = The Journal of Organic Chemistry|date = March 19, 2010|issn = 0022-3263|pages = 1831–1840|volume = 75|issue = 6|doi = 10.1021/jo901503d|first1 = Luis|last1 = Simón|first2 = Jonathan M.|last2 = Goodman|pmid=20039621}} For example, proteases such as chymotrypsin contain an oxyanion hole to stabilise the tetrahedral intermediate anion formed during proteolysis and protects substrate's negatively charged oxygen from water molecules.{{Cite journal|title = Oxyanion Hole Interactions in Serine and Cysteine Proteases|journal = Biological Chemistry Hoppe-Seyler|volume = 373|issue = 2|pages = 393–400|doi = 10.1515/bchm3.1992.373.2.393|year = 1992|last1 = Ménard|first1 = Robert|last2 = Storer|first2 = Andrew C.|pmid = 1387535}} Additionally, it may allow for insertion or positioning of a substrate, which would suffer from steric hindrance if it could not occupy the hole (such as BPG in hemoglobin). Enzymes that catalyse multi-step reactions can have multiple oxyanion holes that stabilise different transition states in the reaction.{{Cite journal|title = The Catalytic Cycle of Biosynthetic Thiolase: A Conformational Journey of an Acetyl Group through Four Binding Modes and Two Oxyanion Holes‡|journal = Biochemistry|date = December 1, 2002|issn = 0006-2960|pages = 15543–15556|volume = 41|issue = 52|doi = 10.1021/bi0266232|first1 = Petri|last1 = Kursula|first2 = Juha|last2 = Ojala|first3 = Anne-Marie|last3 = Lambeir|first4 = Rik K.|last4 = Wierenga|pmid = 12501183}}