Polysaccharide Lyase Family 8 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:18:35Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Michael Suits at 21:30, 21 October 2014

2014-10-21T21:30:24Z

Michael Suits at 20:29, 21 October 2014

2014-10-21T20:29:23Z

Michael Suits at 18:00, 21 October 2014

2014-10-21T18:00:00Z

Michael Suits at 14:47, 3 September 2014

2014-09-03T14:47:54Z

Michael Suits at 14:36, 3 September 2014

2014-09-03T14:36:38Z

Michael Suits at 14:32, 3 September 2014

2014-09-03T14:32:16Z

Wade Abbott at 16:44, 2 September 2014

2014-09-02T16:44:53Z

Wade Abbott at 16:40, 2 September 2014

2014-09-02T16:40:30Z

Michael Suits at 16:33, 14 November 2013

2013-11-14T16:33:42Z

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{UnderConstruction}}
-* [[Author]]: ^^^Michael Suits^^^
+* [[Author]]: [[User:Michael Suits|Michael Suits]]
-* [[Responsible Curator]]:  ^^^Michael Suits^^^
+* [[Responsible Curator]]:  [[User:Michael Suits|Michael Suits]]
 ----

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 |-
 |'''Active site residues'''
-|Try408, His399 (''S. penumoniae'')
+|Known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
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 == Activities and Substrate Specificities ==
-PL8s are active on a  variety of uronic acid-containing polysaccharides including: '''hyaluronan''' (EC 4.2.2.1) [4)-&beta;-D-Glucuronate-1,3-&beta;-D-N-Acetyl-Glucosamine(1]<sub>n</sub>, '''chondroitin AC''' (EC 4.2.2.5) [4)-&beta;-D-Glucuronate-1,3-&beta;-D-N-Acetyl-Galactosamine&Delta;4,6S(1]<sub>n</sub>, '''xanthan''' (EC 4.2.2.12) [4)-&beta;-D-Glucuronate-1,4-&beta;-D-Glucuronate (1]<sub>n</sub>, and '''chondroitin ABC''' (EC 4.2.2.20) [chondroitin AC and chondroitin B (aka. dermatan sulfate: 4)-&beta;-L-Iduronate2S-1,3-&beta;-D-N-Acetyl-Galactosamine4S(1]<sub>n</sub>.
+PL8s are active on a  variety of uronic acid-containing polysaccharides including: hyaluronan (EC 4.2.2.1) [4)-&beta;-D-Glucuronate-1,3-&beta;-D-N-Acetyl-Glucosamine(1]<sub>n</sub>, chondroitin AC (EC 4.2.2.5) [4)-&beta;-D-Glucuronate-1,3-&beta;-D-N-Acetyl-Galactosamine&Delta;4,6S(1]<sub>n</sub>, xanthan (EC 4.2.2.12) [4)-&beta;-D-Glucuronate-1,4-&beta;-D-Glucuronate (1]<sub>n</sub>, and chondroitin ABC (EC 4.2.2.20) [chondroitin AC and chondroitin B (aka. dermatan sulfate: 4)-&beta;-L-Iduronate2S-1,3-&beta;-D-N-Acetyl-Galactosamine4S(1]<sub>n</sub>.
 == Kinetics and Mechanism ==
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 In ''S. pneumoniae'', mutagenesis and kinetic analysis of the HysA mutant suggested three residues were involved in catalysis Asn249, His399, Tyr408 and that two residues, Arg243 and Asn580 were responsible for substrate binding and translocation <cite>Kelly2001</cite>. However, there is some question over what the identity is over the general base (please see Elmabrouk or Zheng ''et al''. for discussions <cite>Elmabrouk2011, Zheng2013</cite>. With respect to chondroitin AC and chondroitin ABC substrate specificity; structural comparisons of the ''Flavobacterium heparinum'' chondroitin AC lyase with the ''Proteus vulgaris'' chondroitin ABC lyase suggests that an Asp444 for an Asn differential in the ''Proteus vulgaris'' active centre provides the mechanism for enzymatic distinguishing between the two epimers <cite>Fethiere1999, Huang2003</cite>.
-== Three-dimensional structures ==
+== Three dimensional structure ==
-'''Structure by Activity''':
+The enzymatic PL8 domain is comprised by an N-terminal α-helical and C-terminal β-sheet domain, which constitute incomplete α<sub>5</sub>/α<sub>5</sub>-barrel and anti-parallel β-sheet structures, respectively. A deep cleft is located in the N-terminal α-helical domain facing the interface between the two domains that accommodates the substrate.
-;Hyaluronan lyase – ''S. pneumoniae'' R6 <cite>Li2000</cite>([{{PDBlink}}1ojm PDB 1OJM]).
-;Chondroitin AC lyase – ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).
+'''Three dimensional structures by activity''':<br/>
-;Xanthan lyase – ''Bacillus'' sp GL1 <cite>Hashimoto2003</cite>([{{PDBlink}}1j0m PDB 1J0M]).
+Chondroitin AC lyase (EC 4.2.2.5) - ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).<br/>
-;Chondroitin ABC lyase – ''P. vulgaris'' <cite>Huang2003</cite>([{{PDBlink}}1hn0 PDB 1HN0]).
+Chondroitin ABC lyase (EC 4.2.2.20) – ''P. vulgaris'' <cite>Huang2003</cite>([{{PDBlink}}1hn0 PDB 1HN0]).<br/>
-;N-terminal Hyaluronan Binding Module – ''S. pneumoniae'' Tigr4 <cite>Suits2014</cite>([{{PDBlink}}4d0q PDB 4D0Q]).
+Hyaluronan lyase (EC 4.2.2.1) – ''S. pneumoniae'' R6 <cite>Li2000</cite>([{{PDBlink}}1ojm PDB 1OJM]).<br/>
 == Family Firsts ==
 ;First catalytic activity: The hydrolysis of hyaluronan was attributed to a pneumococcal hyaluronidase from Pneumococcus type II strain D39R <cite>Rapport1951</cite>.
 ;First 3-D structure: Chondroitin AC lyase – ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).
@@ Line 68: / Line 71: @@
 #Elmabrouk2011 pmid=21287626
 #Zheng2013 pmid=23944739
 #Joshi2009 pmid=19089975

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
-{{CuratorApproved}}
+{{UnderConstruction}}
 * [[Author]]: ^^^Michael Suits^^^
 * [[Responsible Curator]]:  ^^^Michael Suits^^^

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
-{{UnderConstruction}}
+{{CuratorApproved}}
 * [[Author]]: ^^^Michael Suits^^^
 * [[Responsible Curator]]:  ^^^Michael Suits^^^

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 |-
 |'''Charge neutraliser'''
-|His399 (S. pneumoniae)
+|His399 (''S. pneumoniae'')
 |-
 |'''Active site residues'''
-|Try408, His399 (S. penumoniae)
+|Try408, His399 (''S. penumoniae'')
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
@@ Line 36: / Line 36: @@
 == Kinetics and Mechanism ==
-One of the major unresolved controversies around the PL8 catalytic mechanism is the candidate of the general base. Jedrzejas ''et al''. proposed that in the ''Streptococcus pneumoniae'' hyaluronidase, His399 acts as the general base, Asn349 acts to neutralize the C5-carboxylate group, and Tyr408 is the proton donor <cite>Kelly2001, Li2000</cite>. However, for two other PL8 family members: the ''Bacillus'' sp. GL1 xanthanase and ''Streptomyces coelicolor'' A3 hyaluronidase, it was suggested that an equivalent tyrosine residue served as the general acid and general base throughout the reaction <cite>Maruyama2005, Elmabrouk2011</cite>. Combined quantum mechanical and molecular mechanical (QM/MM) simulations suggests the latter hypothesis is favored, with His399 participating in the neutralization of the C5-carboxylate group <cite>Zheng2013</cite>.   Molecular dynamic simulations of the pneumococcal hyaluronidase with hyaluronan fragments suggest that a combination of opening/closing and twisting domain motions of the (α/α)<sub>6</sub> barrel with respect to the anti-parallel β-sheet domain underlies processive substrate translocation <cite>Joshi2009</cite>.
+One of the major unresolved controversies around the PL8 catalytic mechanism is the candidate of the general base. Jedrzejas ''et al''. proposed that in the ''Streptococcus pneumoniae'' hyaluronidase, His399 acts as the general base, Asn349 acts to neutralize the C5-carboxylate group, and Tyr408 is the proton donor <cite>Kelly2001, Li2000</cite>. However, for two other PL8 family members: the ''Bacillus'' sp. GL1 xanthanase and ''Streptomyces coelicolor'' A3 hyaluronidase, it was suggested that an equivalent tyrosine residue served as the general acid and general base throughout the reaction <cite>Maruyama2005, Elmabrouk2011</cite>. Combined quantum mechanical and molecular mechanical (QM/MM) simulations of the ''S. pneumoniae'' enzyme suggests the latter hypothesis is favored, with His399 participating in the neutralization of the C5-carboxylate group <cite>Zheng2013</cite>.   Molecular dynamic simulations of the pneumococcal hyaluronidase with hyaluronan fragments suggest that a combination of opening/closing and twisting domain motions of the (α/α)<sub>6</sub> barrel with respect to the anti-parallel β-sheet domain underlies processive substrate translocation <cite>Joshi2009</cite>.
 == Catalytic Residues ==
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 ;Chondroitin AC lyase – ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).
 ;Xanthan lyase – ''Bacillus'' sp GL1 <cite>Hashimoto2003</cite>([{{PDBlink}}1j0m PDB 1J0M]).
 ;Chondroitin ABC lyase – ''P. vulgaris'' <cite>Huang2003</cite>([{{PDBlink}}1hn0 PDB 1HN0]).
 == Family Firsts ==
-;First catalytic activity: The hydrolysis of hyaluronan was attributed to a pneumococcal hyaluronidase from Pneumococcus type II strain D39R<cite>Rapport1951</cite>.
+;First catalytic activity: The hydrolysis of hyaluronan was attributed to a pneumococcal hyaluronidase from Pneumococcus type II strain D39R <cite>Rapport1951</cite>.
 ;First 3-D structure: Chondroitin AC lyase – ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).
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 #Elmabrouk2011 pmid=21287626
 #Zheng2013 pmid=23944739
 #Joshi2009 pmid=19089975

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 |'''Mechanism'''
 |&beta;-elimination
 |-
 |'''Active site residues'''

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 == Family Firsts ==
 ;First catalytic activity: The hydrolysis of hyaluronan was attributed to a pneumococcal hyaluronidase from Pneumococcus type II strain D39R<cite>Rapport1951</cite>.
-;First catalytic base identification: (Please refer to "Kinetics and Mechanism" and "Catalytic Residue" sections above).
+;First catalytic base identification: Please refer to "Kinetics and Mechanism" and "Catalytic Residues" sections above.
-;First divalent acid identification: (Please refer to "Kinetics and Mechanism" and "Catalytic Residue" sections above).
+;First divalent acid identification: Please refer to "Kinetics and Mechanism" and "Catalytic Residues" sections above.
 ;First 3-D structure: Chondroitin AC lyase – ''F. heparinum'' <cite>Fethiere1999</cite>([{{PDBlink}}1cb8 PDB 1CB8]).