Abstract enzymes for N-glycan biosynthesis

Return a separate collection of simplified N-glycan reaction rules. These enzymes represent reaction activities rather than individual genes. They are never included in db_enzymes(), enzymes_from_rnaseq(), or the default enzyme sets of other functions. Individual activities can also be retrieved by name with enzyme(), for example enzyme("ManII").

Usage

abstract_enzymes(return_str = FALSE)

Arguments

return_str

If FALSE (default), return a named list of enzyme objects. If TRUE, return their activity names, which are accepted by enzyme() and by enzyme or enzymes arguments. An enzymes collection can use activity names or objects, but cannot mix abstract and concrete enzymes.

Value

A named list of glyenzy_abstract_enzyme objects, or a character vector when return_str = TRUE. Each object also inherits from glyenzy_gt_enzyme or glyenzy_gh_enzyme, and glyenzy_enzyme.

Details

The collection contains ManI, GnTI, ManII, GnTII, GnTIII, a6FucT, GnTIV, GnTV, b4GalT, iGnT, a3SiaT, and GlcH: 12 enzymes with 32 reaction rules. All have glycan_type = "N" and species = "unspecified". The additional localization field records "cis", "medial", "trans", or "ER"; it is descriptive and does not impose compartment order during tracing.

The trimming activities follow the corresponding concrete enzymes in the ordinary database. ManI combines the 16 distinct whole-glycan rules of MAN1B1, MAN1A1, MAN1A2, and MAN1C1. ManII uses the shared MAN2A1/MAN2A2 rule, including its core alignment and rejection of bisecting GlcNAc or a galactosylated alpha1-3-arm GlcNAc. It removes either the alpha1-3 or alpha1-6 mannose first, preserving both Man4 intermediates. These rules give the same trimming reactions and network topology as their concrete counterparts; enzyme labels remain abstract.

Core transferase rules also follow the concrete database, including their acceptors, alignment, and rejects: GnTI uses MGAT1; GnTII uses MGAT2; GnTIII uses MGAT3; a6FucT uses FUT8; GnTIV uses MGAT4A/MGAT4B; and GnTV uses the N-glycan rule shared by MGAT5/MGAT5B. The O-mannose-specific MGAT5B rule is not included. GnTIII adds bisecting GlcNAc and has localization = "medial" in this abstract model.

FUT8, MGAT1, and MGAT2 have no explicit rejects in the concrete database; their acceptor and alignment restrictions are retained instead of adding new exclusions. GnTIII rejects galactosylated alpha1-3-arm antennae. GnTIV and GnTV retain their bisecting-GlcNAc and antenna-specific rejects. A reject excludes the matching reaction site, not every site on a glycan.

iGnT rejects the first LacNAc extension on both the beta1-2 and beta1-4 antennae of the alpha1-3 arm, without excluding sites on another arm. Because only iGnT initiates LacNAc extension in this collection, that arm remains unextended in networks generated from the default precursor. The B3GNT4 reject for terminal Gal-GlcNAc-Gal-GlcNAc additionally prevents a second LacNAc extension. Thus the alpha1-6 arm can extend once, but not repeatedly through this activity.

a3SiaT retains the ST3GAL4/ST3GAL6 reject for alpha1-3 fucose on its Gal-GlcNAc acceptor. b4GalT has no explicit reject in the corresponding N-glycan B4GALT rules. Only restrictions for the represented N-glycan activity are imported; unrelated O-glycan and glycolipid reactions are excluded. These terminal activities retain the table acceptors, so this collection is not a replacement for the complete concrete database.

Ambiguous linkages use the existing motif-matching semantics, including potentially compatible reject matches. Product-motif statistics do not apply substrate rejects and do not establish that a product is reachable.

GlcH combines the three glucose-removal steps represented by MOGS and GANAB in the ordinary database. It removes one residue per step from the complete Glc3Man9GlcNAc2 precursor, retaining Glc2 and Glc1 intermediates. Thus the collection can trace from the usual trace_biosynthesis() starting structure without adding ordinary enzymes or changing the start.

Pass activities explicitly, for example enzyme("ManI") to apply_enzyme(), or activity names or the whole list from abstract_enzymes() to trace_biosynthesis(). Abstract reactions are explicit enzyme rules and have is_virtual = FALSE in biosynthesis networks. Existing restrictions on GH involvement statistics and residue matching still apply; this collection does not add GH support to those interfaces.

References

The simplified Golgi rules follow the user-supplied reaction table based on the N-glycosylation model of Spahn et al. (2016), with branch notation described by Liang et al. (2020). The supplied table takes precedence over differences in published versions, except for the concrete trimming and core-transferase rules, added GnTIII activity, and terminal-activity rejects described above. See the bundled rule-data attribution.

Spahn et al. (2016). A Markov chain model for N-linked protein glycosylation. doi:10.1016/j.ymben.2015.10.007 .

Liang et al. (2020). A Markov model of glycosylation elucidates isozyme specificity and glycosyltransferase interactions for glycoengineering. doi:10.1016/j.crbiot.2020.01.001 .

Examples

abstract_enzymes(return_str = TRUE)
#>  [1] "ManI"   "GnTI"   "ManII"  "GnTII"  "GnTIII" "a6FucT" "GnTIV"  "GnTV"  
#>  [9] "b4GalT" "iGnT"   "a3SiaT" "GlcH"  
enzyme("ManII")
#> 
#> ── Enzyme: ManII ───────────────────────────────────────────────────────────────
#> ℹ Type: "GH" (Glycoside hydrolase)
#> ℹ Species: "unspecified"
#> ℹ Glycan type: "N"
#> ℹ Abstract enzyme; localization: "medial"
#> 
#> ── Rules (1) ──
#> 
#> → Rule 1: core alignment
#> Acceptor:
#> "GlcNAc(b1-2)Man(a1-3)[Man(a1-3/6)Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"
#> Product: "GlcNAc(b1-2)Man(a1-3)[Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"
#> Rejects:
#> "GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-4)][Man(a1-3/6)Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"
#> "Gal(b1-4)GlcNAc(b1-2)Man(a1-3)[Man(a1-3/6)Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"

man5 <- paste0(
  "Man(a1-3)[Man(a1-3)[Man(a1-6)]Man(a1-6)]",
  "Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"
)
apply_enzyme(man5, abstract_enzymes()[["GnTI"]])
#> <glycan_structure[1]>
#> [1] GlcNAc(b1-2)Man(a1-3)[Man(a1-3)[Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> # Unique structures: 1
trace_biosynthesis(man5, enzymes = abstract_enzymes(), max_virtual_steps = 0L)
#> IGRAPH 73bc82d DN-- 15 19 -- 
#> + attr: name (v/c), target (v/l), enzyme (e/c), is_virtual (e/l), step
#> | (e/n), enzymes (e/x)
#> + edges from 73bc82d (vertex names):
#> [1] Glc(a1-2)Glc(a1-3)Glc(a1-3)Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-->Glc(a1-3)Glc(a1-3)Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> [2] Glc(a1-3)Glc(a1-3)Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-         ->Glc(a1-3)Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-         
#> + ... omitted several edges