Editing Clostridium perfringens (section)

=== Carbohydrate-active enzymes ===
The human gastrointestinal tract is lined with [[Gastrointestinal wall|intestinal mucosa]] that secrete [[mucus]] and act as a defense mechanism against pathogens, toxins, and harmful substances. Mucus is made up of [[mucin]]s containing several [[O-linked glycosylation|O-linked glycan]] [[glycoprotein]]s that recognizes and forms a barrier around microbes, preventing them from attaching to endothelial cells and infecting them.<ref>{{Cite journal |last1=Ba |first1=Xuli |last2=Jin |first2=Youshun |last3=Ning |first3=Xuan |last4=Gao |first4=Yidan |last5=Li |first5=Wei |last6=Li |first6=Yunhui |last7=Wang |first7=Yihan |last8=Zhou |first8=Jizhang |date=2024-08-07 |title=Clostridium perfringens in the Intestine: Innocent Bystander or Serious Threat? |journal=Microorganisms |language=en |volume=12 |issue=8 |pages=1610 |doi=10.3390/microorganisms12081610 |issn=2076-2607 |pmc=11356505 |pmid=39203452 |doi-access=free}}</ref><ref name=":022">{{Cite journal |last1=Low |first1=Kristin E |last2=Smith |first2=Steven P |last3=Abbott |first3=D Wade |last4=Boraston |first4=Alisdair B |date=2020-05-30 |title=The glycoconjugate-degrading enzymes of ''Clostridium perfringens'': Tailored catalysts for breaching the intestinal mucus barrier |url=https://academic.oup.com/glycob/article/31/6/681/5848600 |journal=Glycobiology |volume=31 |issue=6 |pages=681–690 |doi=10.1093/glycob/cwaa050 |issn=1460-2423 |pmid=32472136|url-access=subscription }}</ref> ''C. perfringens'' can secrete different [[CAZy|carbohydrate-active enzymes]] (CAZymes) that aid in degrading mucins and other O-glycans within the intestinal mucosa. These enzymes include: Sialidases, Hexosaminidases, Galactosidases, and Fucosidases belonging to various [[glycoside hydrolase families]].<ref name=":022" />

==== Sialidase ====
[[Neuraminidase|Sialidases]], also called neuraminidases, function to breakdown mucin by [[Hydrolysis|hydrolyzing]] the terminal sialic acid residues located within the protein through the process of [[Desilylation|desialylation]]. ''C. perfringens'' has three sialidases belonging to [[Glycoside hydrolase family 33|glycoside hydrolase family 33 (GH33)]]: NanH, NanI, and NanJ. All strains of ''C. perfringens'' encode for at least one of these enzymes.<ref name=":022" /><ref>{{Cite journal |last1=Medley |first1=Brendon J. |last2=Low |first2=Kristin E. |last3=Irungu |first3=Jackline D. W. |last4=Kipchumba |first4=Linus |last5=Daneshgar |first5=Parandis |last6=Liu |first6=Lin |last7=Garber |first7=Jolene M. |last8=Klassen |first8=Leeann |last9=Inglis |first9=G. Douglas |last10=Boons |first10=Geert-Jan |last11=Zandberg |first11=Wesley F. |last12=Abbott |first12=D. Wade |last13=Boraston |first13=Alisdair B. |date=2024-10-01 |title=A "terminal" case of glycan catabolism: Structural and enzymatic characterization of the sialidases of Clostridium perfringens |journal=Journal of Biological Chemistry |volume=300 |issue=10 |pages=107750 |doi=10.1016/j.jbc.2024.107750 |doi-access=free |pmid=39251137 |pmc=11525138 |bibcode=2024JBiCh.300j7750M |issn=0021-9258}}</ref>

''C. perfringens'' can secrete NanI and NanJ through secretion signal [[peptide]]s located on each protein. Research suggests that NanH operates in the cytoplasm of ''C. perfringens'', as it does not contain a secretion signal peptide. NanH contains only a catalytic domain, whereas NanI and NanJ contain a [[catalytic domain]] and additional [[carbohydrate-binding module]]s (CBMs) to aid in catalytic activity. Located on their N-terminals, NanI contains CBM40, whereas NanJ contains both CBM40 and CBM32. Based on studies analyzing the three-dimensional structure of NanI, its [[active site]] has a pocket-like orientation that aids in the removal of sialic acid residues from sialomucins in the intestinal mucosa.<ref name=":022" />

==== Hexosaminidase ====
The mucus layer consists of intestinal mucin glycans, glycolipids, and glycoproteins that contain [[hexosamines]], such as [[N-Acetylglucosamine|N-acetylglucosamine]] (GlcNAc) and [[N-Acetylgalactosamine|N-acetylgalactosamine]] (GalNAc). ''C. perfringens'' encodes for eight [[hexosaminidase]]s that break down hexosamines in the mucus. These hexosaminidases belong to four glycoside hydrolase families: GH36, GH84, GH89, and GH123.<ref name=":022" />

''C. perfringens'' encodes for AagA (''Cp''GH36A) and ''Cp''GH36B in [[Glycoside hydrolase family 36|glycoside hydrolase family 36 (GH36)]]: AagA removes GalNAc from O-glycans, and ''Cp''GH36B is expected to have a similar structure to AagA, but specificities on its function are unknown. NagH, NagI, NagJ, and NagK, belonging to glycoside hydrolase family 84 (GH84), cleave terminal GlcNAc residues using a substrate-assisted digestion mechanism. AgnC (''Cp''GH89), belonging to [[glycoside hydrolase family 89]] (GH89), both cleaves GlcNAc from the ends of mucin glycans and acts on gastric mucin. Belonging to glycoside hydrolase family 123 (GH123), ''Cp''Nga123 cleaves GalNAc, but research suggests that it only breaks down glycans taken up by ''C. perfringens'' due to the absence of a secretion signal peptide.<ref name=":022" />

==== Galactosidase ====
''C. perfringens'' has four [[galactosidases]] that belong to the [[glycoside hydrolase family 2|glycoside hydrolase family 2 (GH2)]]: ''Cp''GH2A, ''Cp''GH2B, ''Cp''GH2C, and ''Cp''GH2D. Research suggests that these enzymes are effective at breaking down core mucin glycan structures with the ability to bind [[galactose]] using CBM51. However, minimal research exists on the specific functioning of galactosidases in ''C. perfringens''.<ref name=":022" />

==== Fucosidase ====
[[Fucose]] monosaccharides are located on the terminal ends of core O-linked glycans. ''C. perfringens'' encodes for three fucosidases that belong to two glycoside hydrolase families: Afc1 and Afc2 in [[glycoside hydrolase family 29]] (GH29), and Afc3 in glycoside hydrolase family 95 (GH95). Afc3 contains a C-terminal CBM51 and is the only fucosidase that contains a carbohydrate-binding module in ''C. perfringens''. Fucosyl residues tend to cover the ends of glycans and protect them against enzymatic digestion, so research suggests that the ability of fucosidases to cleave complex and diverse fucosyl linkages is due to long-term adaptations in ''C. perfringens'' that persisted within close range of mucins.<ref name=":022" />