Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158.

Journal of Structural Biology: X(2020)

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摘要
•Side-by-side biochemical comparison of the inhibitors ABH, nor-NOHA and CB-1158.•Arginase-1 binding, inhibition and stabilization by ABH and CB-1158 is pH-dependent.•ABH and CB-1158 have slow association kinetics and a long target residence time.•At higher pH, the catalytic center adopts a more symmetrical coordination structure.•CB-1158 forms an additional hydrogen-bond network in the active site compared to ABH.
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关键词
ABH,nor-NOHA,IC50,KD,Ki,SPR,ITC,KM,kcat,Tm,ΔTm,SD,ka,kd,τ,RMSD,PDB,MQ,DMSO
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