Substrate tunnel regulates substrate specificity switching in hyaluronan synthase Article Swipe
Kaiyi Zhu
,
Yilei Han
,
Yupei Jian
,
Guoqiang Jiang
,
Diannan Lu
,
Jianzhong Wu
,
Zheng Liu
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.10.24.620076
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.10.24.620076
Hyaluronic acid (HA), a ubiquitous linear polysaccharide in the extracellular matrix of vertebrates and the capsule of certain pathogenic bacteria, is characterized by its unique structure of alternating β-1,3- N -acetylglucosamine and β-1,4-glucuronic acid units. HA is synthesized by Class I hyaluronan synthase (HAS) in the majority of organisms, but the molecular mechanisms determining the alternating sequence of HA remain unclear. Here, we demonstrated that HA synthesized in vitro using Streptococcus equisimilis HAS maintained its alternating sequence, regardless of substrate ratios and concentrations. While the active pocket lacks intrinsic selectivity, a distal allosteric regulation from the transmembrane tunnel is revealed. The lingering HA terminals in the active pocket ensure lower binding energies for alternating substrates through Coulombic repulsion and competitive binding. Moreover, the dynamic C-terminal loop at the substrate tunnel entrance reduces transport distance for alternating substrates. Our findings indicate that HA-substrate interactions and enzyme dynamics in the substrate tunnel collectively govern the alternating substrate specificity of HAS. This study provides the first molecular insight into precise substrate specificity control within a single active pocket during template-independent polymer synthesis.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.10.24.620076
- https://www.biorxiv.org/content/biorxiv/early/2024/10/25/2024.10.24.620076.full.pdf
- OA Status
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- References
- 46
- Related Works
- 10
- OpenAlex ID
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Substrate tunnel regulates substrate specificity switching in hyaluronan synthaseWork title
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preprintOpenAlex work type
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enPrimary language
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2024Year of publication
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2024-10-25Full publication date if available
- Authors
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Kaiyi Zhu, Yilei Han, Yupei Jian, Guoqiang Jiang, Diannan Lu, Jianzhong Wu, Zheng LiuList of authors in order
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https://doi.org/10.1101/2024.10.24.620076Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2024/10/25/2024.10.24.620076.full.pdfDirect link to full text PDF
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https://www.biorxiv.org/content/biorxiv/early/2024/10/25/2024.10.24.620076.full.pdfDirect OA link when available
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Substrate (aquarium), Substrate specificity, ATP synthase, Materials science, Cell biology, Biophysics, Chemistry, Enzyme, Biochemistry, Biology, EcologyTop concepts (fields/topics) attached by OpenAlex
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W4386091014, https://openalex.org/W3198134156, https://openalex.org/W3038588865, https://openalex.org/W2789404825, https://openalex.org/W2958685672, https://openalex.org/W4387124262, https://openalex.org/W4220885070, https://openalex.org/W2090556419, https://openalex.org/W2560759054, https://openalex.org/W2121987040, https://openalex.org/W2771023230, https://openalex.org/W2154019529, https://openalex.org/W3210500140, https://openalex.org/W3177828909, https://openalex.org/W4376270962, https://openalex.org/W2944930475, https://openalex.org/W2287905726, https://openalex.org/W4379600532, https://openalex.org/W3046878556, https://openalex.org/W1964320911, https://openalex.org/W2025565866, https://openalex.org/W3036044477, https://openalex.org/W2173417685, https://openalex.org/W2762084119, https://openalex.org/W2588065051, https://openalex.org/W2970676627, https://openalex.org/W3217216416, https://openalex.org/W4322765650, https://openalex.org/W2293812683, https://openalex.org/W4283821741, https://openalex.org/W3036472364, https://openalex.org/W2034008313, https://openalex.org/W2521016898, https://openalex.org/W2208407238, https://openalex.org/W2937662637, https://openalex.org/W4281790889, https://openalex.org/W3168436232, https://openalex.org/W2913977622, https://openalex.org/W2899070097, https://openalex.org/W4288690996, https://openalex.org/W2137825366, https://openalex.org/W2555870966, https://openalex.org/W3148042916, https://openalex.org/W2997849314, https://openalex.org/W2021520922, https://openalex.org/W2170711116 |
| referenced_works_count | 46 |
| abstract_inverted_index.I | 41 |
| abstract_inverted_index.N | 30 |
| abstract_inverted_index.a | 4, 91, 172 |
| abstract_inverted_index.HA | 36, 59, 66, 103 |
| abstract_inverted_index.at | 127 |
| abstract_inverted_index.by | 23, 39 |
| abstract_inverted_index.in | 8, 45, 68, 105, 147 |
| abstract_inverted_index.is | 21, 37, 99 |
| abstract_inverted_index.of | 12, 17, 27, 48, 58, 79, 157 |
| abstract_inverted_index.we | 63 |
| abstract_inverted_index.HAS | 73 |
| abstract_inverted_index.Our | 138 |
| abstract_inverted_index.The | 101 |
| abstract_inverted_index.and | 14, 32, 82, 119, 144 |
| abstract_inverted_index.but | 50 |
| abstract_inverted_index.for | 113, 135 |
| abstract_inverted_index.its | 24, 75 |
| abstract_inverted_index.the | 9, 15, 46, 51, 55, 85, 96, 106, 123, 128, 148, 153, 162 |
| abstract_inverted_index.HAS. | 158 |
| abstract_inverted_index.This | 159 |
| abstract_inverted_index.acid | 2, 34 |
| abstract_inverted_index.from | 95 |
| abstract_inverted_index.into | 166 |
| abstract_inverted_index.loop | 126 |
| abstract_inverted_index.that | 65, 141 |
| abstract_inverted_index.(HA), | 3 |
| abstract_inverted_index.(HAS) | 44 |
| abstract_inverted_index.Class | 40 |
| abstract_inverted_index.Here, | 62 |
| abstract_inverted_index.While | 84 |
| abstract_inverted_index.first | 163 |
| abstract_inverted_index.lacks | 88 |
| abstract_inverted_index.lower | 110 |
| abstract_inverted_index.study | 160 |
| abstract_inverted_index.using | 70 |
| abstract_inverted_index.vitro | 69 |
| abstract_inverted_index.active | 86, 107, 174 |
| abstract_inverted_index.distal | 92 |
| abstract_inverted_index.during | 176 |
| abstract_inverted_index.ensure | 109 |
| abstract_inverted_index.enzyme | 145 |
| abstract_inverted_index.govern | 152 |
| abstract_inverted_index.linear | 6 |
| abstract_inverted_index.matrix | 11 |
| abstract_inverted_index.pocket | 87, 108, 175 |
| abstract_inverted_index.ratios | 81 |
| abstract_inverted_index.remain | 60 |
| abstract_inverted_index.single | 173 |
| abstract_inverted_index.tunnel | 98, 130, 150 |
| abstract_inverted_index.unique | 25 |
| abstract_inverted_index.units. | 35 |
| abstract_inverted_index.within | 171 |
| abstract_inverted_index.binding | 111 |
| abstract_inverted_index.capsule | 16 |
| abstract_inverted_index.certain | 18 |
| abstract_inverted_index.control | 170 |
| abstract_inverted_index.dynamic | 124 |
| abstract_inverted_index.insight | 165 |
| abstract_inverted_index.polymer | 178 |
| abstract_inverted_index.precise | 167 |
| abstract_inverted_index.reduces | 132 |
| abstract_inverted_index.through | 116 |
| abstract_inverted_index.β-1,3- | 29 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.binding. | 121 |
| abstract_inverted_index.distance | 134 |
| abstract_inverted_index.dynamics | 146 |
| abstract_inverted_index.energies | 112 |
| abstract_inverted_index.entrance | 131 |
| abstract_inverted_index.findings | 139 |
| abstract_inverted_index.indicate | 140 |
| abstract_inverted_index.majority | 47 |
| abstract_inverted_index.provides | 161 |
| abstract_inverted_index.sequence | 57 |
| abstract_inverted_index.synthase | 43 |
| abstract_inverted_index.unclear. | 61 |
| abstract_inverted_index.Coulombic | 117 |
| abstract_inverted_index.Moreover, | 122 |
| abstract_inverted_index.bacteria, | 20 |
| abstract_inverted_index.intrinsic | 89 |
| abstract_inverted_index.lingering | 102 |
| abstract_inverted_index.molecular | 52, 164 |
| abstract_inverted_index.repulsion | 118 |
| abstract_inverted_index.revealed. | 100 |
| abstract_inverted_index.sequence, | 77 |
| abstract_inverted_index.structure | 26 |
| abstract_inverted_index.substrate | 80, 129, 149, 155, 168 |
| abstract_inverted_index.terminals | 104 |
| abstract_inverted_index.transport | 133 |
| abstract_inverted_index.C-terminal | 125 |
| abstract_inverted_index.Hyaluronic | 1 |
| abstract_inverted_index.allosteric | 93 |
| abstract_inverted_index.hyaluronan | 42 |
| abstract_inverted_index.maintained | 74 |
| abstract_inverted_index.mechanisms | 53 |
| abstract_inverted_index.organisms, | 49 |
| abstract_inverted_index.pathogenic | 19 |
| abstract_inverted_index.regardless | 78 |
| abstract_inverted_index.regulation | 94 |
| abstract_inverted_index.substrates | 115 |
| abstract_inverted_index.synthesis. | 179 |
| abstract_inverted_index.ubiquitous | 5 |
| abstract_inverted_index.alternating | 28, 56, 76, 114, 136, 154 |
| abstract_inverted_index.competitive | 120 |
| abstract_inverted_index.determining | 54 |
| abstract_inverted_index.equisimilis | 72 |
| abstract_inverted_index.specificity | 156, 169 |
| abstract_inverted_index.substrates. | 137 |
| abstract_inverted_index.synthesized | 38, 67 |
| abstract_inverted_index.vertebrates | 13 |
| abstract_inverted_index.HA-substrate | 142 |
| abstract_inverted_index.collectively | 151 |
| abstract_inverted_index.demonstrated | 64 |
| abstract_inverted_index.interactions | 143 |
| abstract_inverted_index.selectivity, | 90 |
| abstract_inverted_index.Streptococcus | 71 |
| abstract_inverted_index.characterized | 22 |
| abstract_inverted_index.extracellular | 10 |
| abstract_inverted_index.transmembrane | 97 |
| abstract_inverted_index.polysaccharide | 7 |
| abstract_inverted_index.concentrations. | 83 |
| abstract_inverted_index.β-1,4-glucuronic | 33 |
| abstract_inverted_index.-acetylglucosamine | 31 |
| abstract_inverted_index.template-independent | 177 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5100423667 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I99065089 |
| citation_normalized_percentile.value | 0.23705771 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |