biostudies-literaturede Jong NWMZonMw (Netherlands Organization for Health Research and Development)BLRD VANIAID NIH HHSZonMwHHS NIH National Institute of General Medical Sciences (NIGMS)HHS NIH National Institute of Allergy and Infectious Diseases (NIAID)NIGMS NIH HHS2260-2271https://www.ebi.ac.uk/biostudies/studies/S-EPMC5818189biostudies-literatureUnknown293(7)The heme-containing enzyme myeloperoxidase (MPO) is critical for optimal antimicrobial activity of human neutrophils. We recently discovered that the bacterium <i>Staphylococcus aureus</i> expresses a novel immune evasion protein, called SPIN, that binds tightly to MPO, inhibits MPO activity, and contributes to bacterial survival following phagocytosis. A co-crystal structure of SPIN bound to MPO suggested that SPIN blocks substrate access to the catalytic heme by inserting an N-terminal β-hairpin into the MPO active-site channel. Here, we describe a series of experiments that more completely define the structure/function relationships of SPIN. Whereas the SPIN N terminus adopts a β-hairpin confirmation upon binding to MPO, the solution NMR studies presented here are consistent with this rThe Journal of biological chemistryA structurally dynamic N-terminal region drives function of the staphylococcal peroxidase inhibitor (SPIN).PMC5818189GM121511R21 AI111203205200004AI116546R01 GM121511AI111203R01 AI116546I01 BX000513Garcia BLKatz BBHerrera AIPrakash Ovan Strijp JAGGeisbrecht BVvan Kessel KPMde Jong NWMRamyar KXPloscariu NTNauseef WMLeidal KGfalseA structurally dynamic N-terminal region drives function of the staphylococcal peroxidase inhibitor (SPIN).The heme-containing enzyme myeloperoxidase (MPO) is critical for optimal antimicrobial activity of human neutrophils. We recently discovered that the bacterium <i>Staphylococcus aureus</i> expresses a novel immune evasion protein, called SPIN, that binds tightly to MPO, inhibits MPO activity, and contributes to bacterial survival following phagocytosis. A co-crystal structure of SPIN bound to MPO suggested that SPIN blocks substrate access to the catalytic heme by inserting an N-terminal β-hairpin into the MPO active-site channel. Here, we describe a series of experiments that more completely define the structure/function relationships of SPIN. Whereas the SPIN N terminus adopts a β-hairpin confirmation upon binding to MPO, the solution NMR studies presented here are consistent with this r2018-01-01T00:00:00Z2018 Feb2026-04-30T20:24:39.965Z2019-03-26T22:54:58ZS-EPMC58181892930687410.1074/jbc.ra117.00013410.1074/jbc.RA117.000134