Table 2.

Interactions between protein and cofactor and/or substrate

Ring	Wt-Eholo	Interaction	Ring	R173W-ES2	Wt-ES2 (56MR)	Interaction	Mutations
			C1	P101	P101	Pyrrole: π-stack	–
				T102	T102	Ac: H-bond	–
				V215	V215	Pr: H-bond (main chain)	V215E/M	(Bustad et al., 2013; Schneider-Yin et al., 2008)
			C2	S75A	–	Ac: vdW
				K74A	–	Ac: H-bond	–
				–	F77B	Pyrrole: π-stack	–
				K98	K98	N: H-bond (main chain)	K→R	(Kauppinen et al., 1995)
				D99	D99A	Pyrrole: vdW	D→G/H/N	(Floderus et al., 2002; Kauppinen and von und zu Fraunberg, 2002)
				S262	S262	Pr: H-bond	–
					S262B	Ac: H-bond	–
C1	K98	Ac: H-bond	S1	K98	K98	Ac: H-bond	K→R	(Kauppinen et al., 1995)
	D99	N: H-bond		D99	D99	N: H-bond	D→G/H/N	(Floderus et al., 2002; Kauppinen and von und zu Fraunberg, 2002)
	S146	Pr: vdW		–	S146	Pr: vdW	–
	S147 S147	Ac: H-bond Pr: H-bond (main chain)		S147	S147	Ac: H-bond	S→P	(Whatley et al., 2009)
	R149	Ac: Salt bridge		R149	R149	Ac: Salt bridge	R→L/P/Q	(Delfau et al., 1991; Gu et al., 1994; Kauppinen et al., 1995; Yang et al., 2008)
	R150	Pr: Salt bridge		–	–
	R173	Pr: Salt bridge		–	R173	Pr: Salt bridge	R→G/Q/W	(Delfau et al., 1990; Kauppinen et al., 1992; Mendez et al., 2009)
C2	S96	Pr: H-bond	S2	S96	S96	Pr: H bond	S→F	(Kauppinen and von und zu Fraunberg, 2002)
	K98	Ac: H-bond		K98	K98	Ac: H-bond	K→R	(Kauppinen et al., 1995)
	D99	N: H-bond		–	D99A	N: H-bond	D→G/H/N	(Floderus et al., 2002; Kauppinen and von und zu Fraunberg, 2002)
	R150	Pr: Salt bridge		R150	R150	Ac: Salt bridge	–
	A189	Ac: H-bond (main chain)		A189	A189	Ac: H bond (main chain)	–
	R195	Pr: Salt bridge		R195	R195	Pr: salt bridge	R→C/H	(Kauppinen et al., 1995; Whatley et al., 2009)
	Q217	Pr: vdW		–	Q217B	Pr: vdW	Q→H/L/R	(Kuo et al., 2011; Puy et al., 1997; Schneider-Yin et al., 2000, 2006)
				G218	G218	Pr: H bond (main chain)	G→R	(Yang et al., 2008)

^A/BRefers to the subunits of the asymmetric unit in the crystal structure.