Glycoside Hydrolase Family 104

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• Author: ^^^Anthony Clarke^^^
• Responsible Curator: ^^^Anthony Clarke^^^

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Glycoside Hydrolase Family GHnn
Clan	none
Mechanism	retaining
Active site residues	known
CAZy DB link
http://www.cazy.org/fam/GHnn.html

Substrate specificities

Figure 1. Reaction catalyzed by family GH102 enzymes. LT, lytic transglycosylase. (click to enlarge).

The glycoside hydrolases of this family are lytic transglyosylases (also referred to as peptidoglycan lyases) of bacteriophage origin and they constitute family 4 of the classification scheme of Blackburn and Clarke [1]. Unfortunately, the origin of many of the hypothetical enzymes listed in GH104 is misleading because they are encoded within prophages which have been integrated into the chromosome of their bacterial host. In other cases, the phage enzyme has been acquired by pathogenicity islands on the bacterial chromosome. The prototype for this family is the enzyme from lambda phage.

These enzymes cleave the β-1,4 linkage between N-acetylmuramoyl and N-acetylglucosaminyl residues in peptidoglycan (Figure 1). No other activities have been observed.

Kinetics and Mechanism

The lytic transglycosidases, strictly speaking, are retaining enzymes. However, they are not hydrolases but rather catalyse an intramolecular glycosyl transferase reaction onto the C-6 hydroxyl group of the muramoyl residue leading to the generation of a terminal 1,6-anhdyromuramoyl product (Figure 1) thus lacking a reducing end [2]. No detailed analyses involving either steady state or pre-steady state kinetic studies have been reported.

Catalytic Residues

As with other lytic transglycosylases (families GH23, GH102, and GH103), the GH104 enzymes are thought to possess a single catalytic acid/base residue. This residue in lambda phage lytic transglycosylase has been inferred by X-ray crystallography as Glu19 [3]. The mechanism of action of the family GH104 enzymes has not been investigated and thus it is not known if they follow that of the lytic transglycosylases of families GH23, GH102, or GH103.

Three-dimensional structures

The three-dimensional structure of only the lambda phage enzyme has been solved [4], and like the other lytic transglycosylases of families GH23, and GH103, it possesses the well characterized α+β “lysozyme fold.”

Family Firsts

First identification of lytic transglycosylase

MltA from E. coli [2].

First catalytic nucleophile identification

Not applicable for lytic transglycosylases.

First general acid/base residue identification

Inferred by X-ray crystallography of E. coli MltA [4].

First 3-D structure

E. coli MltA [4].

First identification as a lipoprotein

E. coli MltA [5].

First identification of localization to outer membrane

E. coli MltA [5].

Frist demonstration of molecular interactions between GH102 enzymes and penicillin-binding proteins

E. coli MltA [6].

References

1. Blackburn NT and Clarke AJ. (2001). Identification of four families of peptidoglycan lytic transglycosylases. J Mol Evol. 2001;52(1):78-84. DOI:10.1007/s002390010136 |
2. Höltje JV, Mirelman D, Sharon N, and Schwarz U. (1975). Novel type of murein transglycosylase in Escherichia coli. J Bacteriol. 1975;124(3):1067-76. DOI:10.1128/jb.124.3.1067-1076.1975 |
3. Leung AK, Duewel HS, Honek JF, and Berghuis AM. (2001). Crystal structure of the lytic transglycosylase from bacteriophage lambda in complex with hexa-N-acetylchitohexaose. Biochemistry. 2001;40(19):5665-73. DOI:10.1021/bi0028035 |