Proposals for the urease catalytic mechanism. (A) The hydroxyl group bound to Ni-2 attacks urea, whose carbonyl group is polarized by coordination to Ni1, forming a tetrahedral intermediate that releases ammonia with His 320 (K. aerogenes numbering) acting as a general acid. (B) The bridging hydroxyl group attacks urea, bound with its carbonyl group coordinated to Ni1 and an amine interacting with Ni2, and the hydroxyl proton transfers to the released ammonia. (C) A merged mechanism in which the bridging water attacks the substrate, but with His 320 acting as a general acid. (D) Elimination mechanism to form a cyanic acid (O=C=N-H) intermediate that subsequently becomes hydrated (not depicted) to form carbamate. In all mechanisms, the carbamate spontaneously decomposes.