Residue L143 of the foot-and-mouth disease virus leader proteinase is a determinant of cleavage specificity.
The foot-and-mouth disease virus (FMDV) leader proteinase (L(pro)) self-processes inefficiently at the L(pro)/VP4 cleavage site LysLeuLys*GlyAlaGly (* indicates cleaved peptide bond) when the leucine at position P2 is replaced by phenylalanine. Molecular modeling and energy minimization identified the L(pro) residue L143 as being responsible for this discrimination. The variant L(pro) L143A self-processed efficiently at the L(pro)/VP4 cleavage site containing P2 phenylalanine, whereas the L143M variant did not. L(pro) L143A self-processing at the eIF4GII sequence AspPheGly*ArgGlnThr was improved but showed more-extensive aberrant processing. Residue 143 in L(pro) is occupied only by leucine and methionine in all sequenced FMDV serotypes, implying that these bulky side chains are one determinant of the restricted specificity of L(pro).
Mayer
Christina
C
Medical University of Vienna, Max F. Perutz Laboratories, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Neubauer
David
D
Nchinda
Aloysius T
AT
Cencic
Regina
R
Trompf
Katja
K
Skern
Tim
T
D000595:Amino Acid Sequence; D000818:Animals; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000201:enzymology*; D006868:Hydrolysis; D007930:Leucine; D008958:Models, Molecular; D020125:Mutation, Missense; D013379:Substrate Specificity / Q000235:genetics
D010450:Endopeptidases; D007930:Leucine