Jedrzejas Mark J, Stern Robert
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Proteins. 2005 Nov 1;61(2):227-38. doi: 10.1002/prot.20592.
Human hyaluronidases (Hyals) are a group of five endo-beta-acetyl-hexosaminidase enzymes, Hyal-1, -2, -3, -4, and PH-20, which degrade hyaluronan using a hydrolytic mechanism of action. Catalysis by these Hyals has been shown to follow a double-displacement scheme. This involves a single Glu residue within the enzyme, the only catalytic residue, as the proton donor (acid). Also involved is a carbonyl group of the hyaluronan (HA) N-acetyl-D-glucosamine as a unique type of nucleophile. Thus the substrate participates in the mechanism of action of its own catalysis. An oxocarbonium ion transition state is postulated, but there is no formation of a covalent enzyme-glycan intermediate, as found in most such reactions. The major domain is catalytic and has a distorted (beta/alpha)8 triose phosphate isomerase (TIM) barrel fold. The C-terminal domain is separated by a peptide linker. Each Hyal has a different C-terminal sequence and structure, the function of which is unknown. These unique C-termini may participate in the additional function(s) associated with these multifunctional enzymes.
人透明质酸酶（Hyal）是一组由五种内切β-乙酰己糖胺酶组成的酶，即Hyal-1、-2、-3、-4和PH-20，它们通过水解作用机制降解透明质酸。已证明这些Hyal的催化作用遵循双置换机制。这涉及到酶内的单个Glu残基，即唯一的催化残基，作为质子供体（酸）。还涉及透明质酸（HA）N-乙酰-D-葡萄糖胺的羰基作为一种独特类型的亲核试剂。因此，底物参与了其自身催化的作用机制。假定存在氧鎓离子过渡态，但不像大多数此类反应那样形成共价酶-聚糖中间体。主要结构域具有催化作用，并且具有扭曲的（β/α）8磷酸丙糖异构酶（TIM）桶状折叠。C末端结构域由一个肽接头隔开。每种Hyal都有不同的C末端序列和结构，其功能尚不清楚。这些独特的C末端可能参与了与这些多功能酶相关的其他功能。
