. Author manuscript; available in PMC: 2020 May 7.

Published in final edited form as: Structure. 2019 Mar 21;27(5):794–805.e4. doi: 10.1016/j.str.2019.03.002

Table 2.

Comparison of Human SQOR with Bacterial H₂S-Oxidizing Enzymes

	Structural Comparison			Electrostatics		Distance (Å)				Active-Site Accessibility
Protein (pdb code)	RMSD (Å)	No. of C^α Matches	FAD Attachment	Net Charge (pl)^a	Membrane- vs Solvent-Facing Surfaces^b	Cys^P:SG to Cys^D:SG^c	FAD:C4a to		Loop Above re-face of FAD^d	re-face of FAD	Active-Site Cysteines
Protein (pdb code)	RMSD (Å)	No. of C^α Matches	FAD Attachment	Net Charge (pl)^a	Membrane- vs Solvent-Facing Surfaces^b	Cys^P:SG to Cys^D:SG^c	Cys^P:SG	Cys^D:SG	Loop Above re-face of FAD^d	re-face of FAD	Active-Site Cysteines
Human SQOR (PDB: 6MO6)	–	–	noncovalent	positive (9.02)	polarized	3.4	3.5		P195-G203	obstructed	Cys^D: close to the surface, accessible via a short channel; Cys^P: shielded

A. vinosum FCSD (PDB: 1fcd)	2.60	245	covalent^e	negative (5.28)	NA	2.1	3.3		P154-P162	obstructed	on the surface, solvent exposed

T. tepidum FCSD (PDB: 3vrd)	2.61	241	covalent^e	negative (5.55)	NA	4.9	3.5		P154-P162	obstructed	on the surface, solvent exposed

T. paradoxus FCSD (PDB: 5n1t)	2.58	239	covalent^e	negative (5.53)	NA	4.7	3.5		P186-P194	obstructed	on the surface, solvent exposed

A. aeolicus SQOR (PDB: 3hyw)	2.25	212	covalent^e	negative (6.53)	polarized	8.1, 8.3, 9.0, 9.3^f	6.1, 6.2^f	5.7, 6.9^f	I151-C156	accessible cavity, accommodates sulfur polymerization products	accessible via channels

A. ferrooxidans SQOR (PDB: 3t31)	2.91	248	noncovalent	negative (6.48)	polarized	6.7, 6.8^g	6.0	4.7, 5.2^g	M155-C160	partially shielded, but solvent accessible	accessible via channels

A. ambivalens SQOR (PDB: 3h8l)	2.11	221	covalent^e	negative (6.33)	ND	6.5, 7.1^g	4.9	7.4, 7.6^g	G154-E179	partially shielded, but solvent accessible	accessible via a channel

Net charge at pH 7.4 estimated based on the calculated isoelectric point (pI).

Solvent refers to the inner mitochondrial matrix (human SQOR) or the periplasmic space (bacterial SQORs), respectively. The property is not applicable (NA) for FCSDs, which are soluble proteins. Electrostatic surface properties were not determined (ND) for A. ambivalens SQOR because no interpretable electron density was observed for the C-terminal membrane-binding domain.

The proximal active-site cysteine (Cys^P) is closer to the N terminus of the protein than the distal cysteine (Cys^D). Cys^P:SG is also closer to FAD:C4a in human SQOR, FCSD and some bacterial SQORs. (Cys^P) = Cys201 (human); Cys161 (A. vinosum FCSD); Cys161 (T. tepidum FCSD); Cys193 (T. paradoxus FCSD); Cys156 (A. aeolicus SQOR); Cys160 (A. ferrooxidans SQOR); Cys178 (A. ambivalens SQOR). Cys^D = Cys379 (human); Cys337 (A. vinosum FCSD); Cys337 (T. tepidum FCSD); Cys364 (T. paradoxus FCSD); Cys347 (A. aeolicus SQOR); Cys356 (A. ferrooxidans SQOR); Cys350 (A. ambivalens SQOR).

The loop from the second Rossmann fold in human SQOR, FCSDs and bacterial SQOR’s includes Cys^P.

Thioether link between FAD:C8M and a cysteine residue: Cys42, A. vinosum FCSD; Cys42, T. tepidum FCSD; Cys73, T. paradoxus FCSD; Cys124, A. aeolicus SQOR; Cys129, A. ambivalens SQOR.

Two alternate conformations are observed for both Cys^P and Cys^D.

Two alternate conformations are observed for Cys^D.