An oxyanion hole is a pocket in the
active site of an
enzyme that stabilizes
transition state negative charge on a
deprotonatedoxygen or
alkoxide.[1] 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.[2] 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.[3] 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.[4]
^Simón, Luis; Goodman, Jonathan M. (March 19, 2010). "Enzyme Catalysis by Hydrogen Bonds: The Balance between Transition State Binding and Substrate Binding in Oxyanion Holes". The Journal of Organic Chemistry. 75 (6): 1831–1840.
doi:
10.1021/jo901503d.
ISSN0022-3263.
PMID20039621.
^Ménard, Robert; Storer, Andrew C. (1992). "Oxyanion Hole Interactions in Serine and Cysteine Proteases". Biological Chemistry Hoppe-Seyler. 373 (2): 393–400.
doi:
10.1515/bchm3.1992.373.2.393.
PMID1387535.
^Kursula, Petri; Ojala, Juha; Lambeir, Anne-Marie; Wierenga, Rik K. (December 1, 2002). "The Catalytic Cycle of Biosynthetic Thiolase: A Conformational Journey of an Acetyl Group through Four Binding Modes and Two Oxyanion Holes‡". Biochemistry. 41 (52): 15543–15556.
doi:
10.1021/bi0266232.
ISSN0006-2960.
PMID12501183.