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Devastating Degradations: Hya and PLA's “Inflammous Plot”
Author(s) -
Ross Khadiyah,
Lam Emily,
Graham Eric,
Moore Melshae,
Wofford Ayanna,
Pharr Carmen,
JohnsonAnthony Chasity,
Stubbs Tamica,
Colton Shan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb228
Subject(s) - chemistry , hyaluronidase , biochemistry , bee venom , glycosidic bond , snake venom , venom , enzyme , biology , zoology
According to the CDC, 90–100 Americans stung by bees annually die due to anaphylactic shock. Using 3D printing technology, the Berry Academy SMART Team (Students Modeling a Research Topic) modeled two proteins in bee venom: hyaluronidase (Hya), a TIM barrel structured enzyme, and bee venom phospholipase (PLA 2 ). Hya and PLA 2 work in tandem to spread bee venom by degrading the extracellular matrix (ECM) and disrupting cellular membranes, respectively. Hya begins degradation by binding to and cleaving hyaluronic acid (HA), a glycosaminoglycan made of repeating disaccharide (GlcNac and GlcA) units in the ECM that facilitate tissue stabilization. Arg116 and Arg224 guide HA to the active site, where HA binds to Ser304, Ser303, Tyr227, and Asp111. Hya cleaves glycosidic bonds within HA, mediated by Glu113, thus degrading the ECM and allowing PLA 2 to access to membrane's lipids. Once exposed, PLA 2 mediates the hydrolysis of phospholipids by attacking the sn‐2 acyl‐bond of phospholipids through polarization of sn‐2 to sequestrate catalytic H 2 O (W 5 ) and abridgment of W 5 to W 6 by His34, which then is neutralized by Asp35 and Asp64. This cleavage reaction releases archindonate products, which incite inflammatory responses, leading to the pain and swelling associated with bee stings. Understanding how these proteins function may help to improve anti‐venom medicines. Supported by a grant from the NIH‐CTSA UL1RR031973.