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MppP: The Beginning of L‐End (Synthesis)
Author(s) -
Tiffany Karen,
Amundson Jacob,
Boeselager Amy,
Bote Kayla,
Burgarino Michael,
Burns Riley,
Ertl Ellie,
Fairchild Elliott,
Fueger Kaitlyn,
Garey Simon,
Going Julia,
Ketelhohn Amelia,
Kubiak Katelyn,
Kunz Josslyne,
Langholz Andrew,
Levy Sara,
Novack Maya,
Phelps Katelyn,
Remington Erika,
Schoenberg Spencer,
Tiffany Benjamin,
Silvaggi Nicholas
Publication year - 2019
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.2019.33.1_supplement.lb221
Subject(s) - active site , chemistry , stereochemistry , biosynthesis , cofactor , catalysis , enzyme , oxidase test , protein structure , biochemistry , combinatorial chemistry
Infections caused by antibiotic‐resistant pathogens like MRSA are serious problems that require the development of new antibiotics. The non‐proteinogenic amino acid L‐enduracididine (L‐End) is looked at as a solution, as it could be used to synthesize new versions of L‐End‐containing antibiotics and improve drug efficacy of antibiotics not normally containing L‐End. However, L‐End is difficult to synthesize and is not commercially available. The enzyme MppP, an L‐arginine deaminase/hydroxylase from Streptomyces wadayamensis , is involved in L‐Arg biosynthesis. MppP is a pyridoxal 5′‐phosphate (PLP)‐dependent oxidase catalyzing the oxidation of L‐Arg to 2‐oxo‐4‐hydroxy‐guanidinovaleric acid, which continues along the pathway to produce L‐End. Four electrons are transferred to L‐Arg from molecular oxygen via the PLP cofactor; water contributes the hydroxyl and ketone oxygen atoms of the product. MppP functions as a homodimer. Each 376‐residue protomer contains a large domain, primarily composed of beta sheets, and a smaller domain consisting of a mix of alpha helices and beta sheets. The active site, containing PLP and the catalytic Lys221, is located between these two domains. The N‐terminal portion of the protein is not ordered unless substrate or product is bound in the active site, and this region appears to be critical for catalysis. The Cedarburg SMART (Students Modeling A Research Topic) Team has designed a model of MppP using 3D printing technology to investigate MppP structure‐function relationships. Studying the structure and function of MppP can elucidate the mechanism of L‐End biosynthesis, making possible the commercial production of L‐End for use in new MRSA‐fighting antibiotics. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .