TY - JOUR
T1 - Promiscuous binding in a selective protein
T2 - The bacterial NA +/H + antiporter
AU - Alhadeff, Raphael
AU - Ganoth, Assaf
AU - Krugliak, Miriam
AU - Arkin, Isaiah T.
PY - 2011/10/12
Y1 - 2011/10/12
N2 - The ability to discriminate between highly similar substrates is one of the remarkable properties of enzymes. For example, transporters and channels that selectively distinguish between various solutes enable living organisms to maintain and control their internal environment in the face of a constantly changing surrounding. Herein, we examine in detail the selectivity properties of one of the most important salt transporters: the bacterial NA +/H + antiporter. Selectivity can be achieved at either the substrate binding step or in subsequent antiporting. Surprisingly, using both computational and experimental analyses synergistically, we show that binding per se is not a sufficient determinant of selectively. All alkali ions from Li + to Cs + were able to competitively bind the antiporter's binding site, whether the protein was capable of pumping them or not. Hence, we propose that NhaA's binding site is relatively promiscuous and that the selectivity is determined at a later stage of the transport cycle.
AB - The ability to discriminate between highly similar substrates is one of the remarkable properties of enzymes. For example, transporters and channels that selectively distinguish between various solutes enable living organisms to maintain and control their internal environment in the face of a constantly changing surrounding. Herein, we examine in detail the selectivity properties of one of the most important salt transporters: the bacterial NA +/H + antiporter. Selectivity can be achieved at either the substrate binding step or in subsequent antiporting. Surprisingly, using both computational and experimental analyses synergistically, we show that binding per se is not a sufficient determinant of selectively. All alkali ions from Li + to Cs + were able to competitively bind the antiporter's binding site, whether the protein was capable of pumping them or not. Hence, we propose that NhaA's binding site is relatively promiscuous and that the selectivity is determined at a later stage of the transport cycle.
UR - http://www.scopus.com/inward/record.url?scp=80053994565&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0025182
DO - 10.1371/journal.pone.0025182
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C2 - 22022382
AN - SCOPUS:80053994565
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e25182
ER -