Modulating the pH Activity Profiles of Phenylalanine Ammonia Lyase from Anabaena variabilis by Modification of Center-Near Surface Residues View Full Text


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Article Info

DATE

2017-11

AUTHORS

Fan Zhang, Nan Huang, Li Zhou, Wenjing Cui, Zhongmei Liu, Longbao Zhu, Yi Liu, Zhemin Zhou

ABSTRACT

Phenylalanine ammonia lyase from Anabaena variabilis (Av-PAL) is a candidate for the treatment of phenylketonuria (PKU). However, Av-PAL shows its optimal pH at 8.5 and maintains only 70% of its highest activity when pH decreases to 7.3-7.4 (the condition of human plasma). The objective of the study was to shift its optimal pH by mutating surface amino acid residues which interact with the general base Tyr78. Based on the crystal structure and the online program GETAREA, we selected five sites: Asn69, Glu72, Glu75, Asn89, and Val90. Removing negative charges or introducing positive charges near the general base Tyr78 by mutation, the pH optima were successfully shifted to more acidic range. Especially, the pH optima of E75A, E75L, and E75Q were shifted to 7.5 with 35, 30, and 24% higher specific activities than that of the wild, respectively. Half-lives of E75L and E75Q at 70 °C prolonged to 190 and 180 min from 130 min of the wild, respectively. In addition, the higher resistance to a low pH of 3.5 and protease made E75L a candidate for oral medicine of PKU. This work would improve the therapeutic prospect of Av-PAL and provide guidance in modulating optimal pH of enzymes. More... »

PAGES

699-711

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12010-017-2458-8

DOI

http://dx.doi.org/10.1007/s12010-017-2458-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084033654

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28343264


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s12010-017-2458-8'


 

This table displays all metadata directly associated to this object as RDF triples.

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