Structural modelling of the lumenal domain of human GPAA1, the metallo-peptide synthetase subunit of the transamidase complex, reveals zinc-binding mode and two flaps surrounding the active site

Table 1 Summary of Zn-binding sites of structures used in the 3D structure modelling in this study

Structure	Site 1	Site 2	Site 3	Site 4	Site 5	Coordinated metal ions	Substrate	Ref.
4f9u	–	Asp⁹⁹	Glu¹³⁹	–	His²⁶⁵	Zn	SUB1	[30]
	His⁸²	–	–	Asp¹⁸⁶		no 2nd ion
4fwu	–	Asp⁹⁹	Glu¹³⁹	–	His²⁶⁵	Zn	no substrate	[31]
	His⁸²	–	–	Asp¹⁸⁶	–	no 2nd ion
1f2o		Asp⁹⁷	Glu¹³²	–	His²⁴⁷	Zn1	SUB2	[32]
	His⁸⁵	Asp⁹⁷	–	Asp¹⁶⁰	–	Zn2
1amp		Asp¹¹⁷	Glu¹⁵²	–	His²⁵⁶	Zn1	No substrate	[28]
	His⁹⁷	Asp¹¹⁷	–	Asp¹⁷⁹	–	Zn2
GAA1^Zn	–	Asp¹⁵³	Asp¹⁸⁸	–	Tyr³⁵⁸	Zn	PEP or SUB1	(model / this work)
	*Pro¹⁴⁹		–	Glu²²⁶	–	no 2nd ion
GAA1^Zn1Zn2	–	Asp¹⁵³	Asp¹⁸⁸	–	Tyr³⁵⁸	Zn1	PEP or SUB2	(model / this work)
	*Pro¹⁴⁹	Asp¹⁵³	–	Glu²²⁶	–	Zn2

This table lists all the amino acid residues involved in the metal ion binding as well as the type of model substrates in the X-ray crystallographic 3D (including references) and model structures used in this work. Residue numbering follows the nomenclature in the published crystal structures and, for GPAA1, in UniProt sequence entry O43292. SUB1 stands for 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]-thiourea [30] and SUB2 is the label for L-leucine [32]. PEP is described in the text and in Fig. 1
*Proline 84 (site 1) does not bind to a Zn ion

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