CsdA cysteine desulfurase (the sulfur donor) and the CsdE sulfur acceptor are involved in biological sulfur trafficking and in iron sulfur cluster assembly in the model bacterium Escherichia coli. CsdA and CsdE form a stable complex through a polar interface that includes CsdA Cys328 and CsdE Cys61, the two residues known to be involved in the sulfur transfer reaction. Although mechanisms for the transfer of a sulfur moiety across protein protein interfaces have been proposed based on the IscS IscU and IscS TusA structures, the flexibility of the catalytic cysteine loops involved has precluded a high resolution view of the active-site geometry and chemical environment for sulfur transfer. Here, we have used a combination of X-ray crystallography, solution NMR and SAXS, isothermal calorimetry, and computational chemistry methods to unravel how CsdA provides a specific recognition platform for CsdE and how their complex organizes a composite functional reaction environment. The X-ray structures of persulfurated (CsdA)(2) and persulfurated (CsdA-CsdE)(2) complexes reveal the crucial roles of the conserved active-site cysteine loop and additional catalytic residues in supporting the transpersulfuration reaction. A mechanistic view of sulfur transfer across protein protein interfaces that underpins the requirement for the conserved cysteine loop to provide electrostatic stabilization for the in-transfer sulfur atom emerges from the analysis of the persulfurated (CsdA-CsdE)(2) complex structure.