Glycoside Hydrolase Family 105

This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

• Author: ^^^James Stevenson^^^
• Responsible Curator: ^^^Joel Weadge^^^

---

Glycoside Hydrolase Family GH105
Clan	GH-x
Mechanism	retaining/inverting
Active site residues	known/not known
CAZy DB link
https://www.cazy.org/GH105.html

Substrate specificities

GH105 enzymes are a class of unsaturated glucuronyl/galacturonyl hydrolases found mainly in bacteria, but a few fungial and a handful of archaeal enzymes have also been annotated [1]. Much like the glycoside hydrolase family 88, enzymes from GH105 perform hydrolysis via a hydration of the double bond between the C-4 and C-5 carbons of the terminal monosaccharide of their substrates [2, 3]. Enzymes from GH105 have been organized into three subgroups: unsaturated rhamnogalacturonidases, d-4,5-unsaturated β-glucuronyl hydrolases, and d-4,5-unsaturated α-galacturonidases. The unifying feature shared between these substrates is the presence of the non-reducing monosaccharide 4-deoxy-L-threo-hex-4-enopyranuronosyl that binds at the -1 active site of the enzymes, and is linked to the +1 sugar via its anomeric C-1 carbon. The 4-deoxy-L-threo-hex-4-enopyranuronosyl saccharide is defined as ΔGal or ΔGlc depending on whether it assumes an α- or β- configuration, respectively. In degradable substrates, the sugar present at the +1 position can be linked via its C-2, C-4, or C-6 carbon, given the substrate preference of individual enzymes [2, 4]. Some of the various carbohydrate sources targeted by GH105 enzymes include: rhamnogalacturonan-I, ulvan, and the arabinogalactan decoration on certain cell wall proteins [2, 5, 6, 7].

Kinetics and Mechanism

GH105 enzymes do not act via a typical Koshland retaining or inverting mechanism [8], rather the current proposed mechanism of action for these enzymes is hydrolysis through syn-hydration of the double bond between the C-4 and C-5 carbons of the enopyranuronosyl residue of their substrate [5]. This hydration reaction forms a hemiketal that undergoes spontaneous rearrangement to form an intermediate hemiacetyl, which undergoes another rearrangement resulting in the breakage of the bond to the neighbouring saccharide(at the +1 subsite of the enzyme) of the polymer. This mechanism was initially theorized based on the oligosaccharide and amino acid arrangement in a substrate-bound crystal structure [6], but has been confirmed through kinetic isotope effects and NMR analysis in the highly related unsaturated glucuronyl hydrolase GH88 family [3, 9].

The kinetics for three enzymes from this family have been determined, two from B. subtilis and one from B. thetaiotaomicron. YteR from B. subtilis was found to have a kcat and KM of 0.2±0.011s-1 and 100±14μM, respectively, against the substrate ΔGal-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7s-1 and 719±75μM for kcat and KM, respectively, with the same substrate [6]. BT3687 from B. thetaiotaomicron was determined to have a kcat of 0.59±0.057s-1 and a KM of 71.87±12.51μM against the substrate ΔGlc-GlcNAc [2].

Although it is atypical for a glycoside hydrolase family to contain enzymes capable of degrading both α- or β-linked substrates, this has also been observed in other families that deviate significantly from typical acid-base mechanisms(eg. GH3, GH4) [10].

Catalytic Residues

Content is to be added here.

Three-dimensional structures

Content is to be added here.

Family Firsts

First stereochemistry determination

Content is to be added here.

First catalytic nucleophile identification

Content is to be added here.

First general acid/base residue identification

Content is to be added here.

First 3-D structure

Content is to be added here.

References

1. Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, and Henrissat B. (2009). The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2009;37(Database issue):D233-8. DOI:10.1093/nar/gkn663 |
2. Munoz-Munoz J, Cartmell A, Terrapon N, Baslé A, Henrissat B, and Gilbert HJ. (2017). An evolutionarily distinct family of polysaccharide lyases removes rhamnose capping of complex arabinogalactan proteins. J Biol Chem. 2017;292(32):13271-13283. DOI:10.1074/jbc.M117.794578 |
3. Jongkees SA and Withers SG. (2011). Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases. J Am Chem Soc. 2011;133(48):19334-7. DOI:10.1021/ja209067v |
4. Zhang R, Minh T, Lezondra L, Korolev S, Moy SF, Collart F, and Joachimiak A. (2005). 1.6 A crystal structure of YteR protein from Bacillus subtilis, a predicted lyase. Proteins. 2005;60(3):561-5. DOI:10.1002/prot.20410 |
5. Itoh T, Ochiai A, Mikami B, Hashimoto W, and Murata K. (2006). Structure of unsaturated rhamnogalacturonyl hydrolase complexed with substrate. Biochem Biophys Res Commun. 2006;347(4):1021-9. DOI:10.1016/j.bbrc.2006.07.034 |
6. Itoh T, Ochiai A, Mikami B, Hashimoto W, and Murata K. (2006). A novel glycoside hydrolase family 105: the structure of family 105 unsaturated rhamnogalacturonyl hydrolase complexed with a disaccharide in comparison with family 88 enzyme complexed with the disaccharide. J Mol Biol. 2006;360(3):573-85. DOI:10.1016/j.jmb.2006.04.047 |
7. Collén PN, Jeudy A, Sassi JF, Groisillier A, Czjzek M, Coutinho PM, and Helbert W. (2014). A novel unsaturated β-glucuronyl hydrolase involved in ulvan degradation unveils the versatility of stereochemistry requirements in family GH105. J Biol Chem. 2014;289(9):6199-211. DOI:10.1074/jbc.M113.537480 |

8. Koshland, D.E. (1953) Stereochemistry and the Mechanism of Enzymatic Reactions. Biological Reviews, vol. 28, no. 4., pp. 416-436. [1].

9. Jongkees SAK, Yoo H, and Withers SG. (2014). Mechanistic investigations of unsaturated glucuronyl hydrolase from Clostridium perfringens. J Biol Chem. 2014;289(16):11385-11395. DOI:10.1074/jbc.M113.545293 |
10. Rye CS and Withers SG. (2000). Glycosidase mechanisms. Curr Opin Chem Biol. 2000;4(5):573-80. DOI:10.1016/s1367-5931(00)00135-6 |
11. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, and Ferrin TE. (2004). UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605-12. DOI:10.1002/jcc.20084 |

12. JointCenterforStructuralGenomics(JCSG) (2009) Crystal structure of Putative glycosyl hydrolase (NP_813087.1) from BACTEROIDES THETAIOTAOMICRON VPI-5482 at 1.80 A resolution. RCSB Protein Data Bank. [1].

13. Osipiuk, J., Li, H., Endres, M., Joachimiak, A. (2014) Glycosyl hydrolase family 88 from Bacteroides vulgatus. RCSB Protein Data Bank. [1].

14. Germane KL, Servinsky MD, Gerlach ES, Sund CJ, and Hurley MM. (2015). Structural analysis of Clostridium acetobutylicum ATCC 824 glycoside hydrolase from CAZy family GH105. Acta Crystallogr F Struct Biol Commun. 2015;71(Pt 8):1100-8. DOI:10.1107/S2053230X15012121 |

15. Tan, K., Hatzos-Skintges, C., Bearden, J., Joachimiak, A. (2010) The crystal structure of a possible member of GH105 family from Klebsiella pneumoniae subsp. pneumoniae MGH 78578. RCSB Protein Data Bank. [1].

16. Tan, K., Hatzos-Skintges, C., Bearden, J., Joachimiak, A. (2011) The crystal structure of a possible member of GH105 family from Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150. RCSB Protein Data Bank. [1].

17. Stogios, P.J., Xu, X., Cui, H., Yim, V., Savchenko, A. (2015) Crystal structure of a glycoside hydrolase family 105 (GH105) enzyme from Thielavia terrestris. RCSB Protein Data Bank. [1].