[28]
OVERVIEW OF IRON-SULFUR PROTEINS
259
[28] O v e r v i e w of I r o n - S u l f u r P r o t e i n s B y W. H. ORME-JOHNSON and N. R. ORME-JOHNSON
Definition, N o m e n c l a t u r e , a n d P r o p e r t i e s 1 I r o n - s u l f u r proteins are those in which iron is bound via sulfur-containing ligands. We exclude f r o m consideration hemoproteins, such as c y t o c h r o m e c (and p r e s u m a b l y c y t o c h r o m e P-450), which contain axial sulfur ligands. Figure 1 gives a classification scheme for iron proteins that emphasizes the varieties of Fe-S proteins presently recognized. The group of Fe-S proteins denoted " s i m p l e " , which contain no recognized prosthetic groups other than Fe-S clusters, a p p e a r to function mainly as electron carriers. Useful physical properties of representative m e m b e r s of this group are listed in Table I. The study of this type of protein and a series of synthetic analogs 2 of the iron-sulfur clusters in these proteins led to the conclusion 3 that three types of Fe-S centers in proteins are as depicted in Fig. 2. In addition to the n u m b e r of iron a t o m s present in one of these centers, one needs to specify the oxidation state, which is generally indicated by the net charge state, c o m p u t e d on the assumption that the cysteines are formally present as mercaptide, the labile sulfur as sulfide, and the iron a t o m s as the formally ferric or ferrous state. F o r the k n o w n types of clusters, the oxidation states so far recognized in proteins are shown in Table II. It should be borne in mind that electrochemical studies 2 show that other net charge states of the clusters are possible (although they have not yet been recognized in proteins), and also that there m a y be other types of Fe-S centers in proteins. As shown in Tables I - I I I the high-potential i r o n - s u l f u r proteins and the bacterial-type ferredoxins, each of which contains 4-Fe clusters, differ by which pair of oxidation states are utilized. 4 i Most of the material in this section is adapted from a report (1976) by a subcommittee (H. Beinert, Chairman, R. Cammack, R. H. Holm, L. H. Jensen, J. Kraut, W. Lovenberg, W. H. Orme-Johnson, J. C. Rabinowitz, and E. C. Slater) of the IUPAC--IUB Commission on Biochemical Nomenclature, in which recommendations for the nomenclature of iron-sulfur We-S) proteins are made. Here we give a very brief summary of these recommendations. z R. H. Holm and J. A. lbers, in "Iron-Sulfur Proteins" (W. Lovenberg, ed.), Vol. 3, p. 206. Academic Press, New York, 1977; and references therein. 3 W. H. Orme-Johnson, Annu. Rev. Biochem. 42, 159 (1973); and references therein. 4 T. Herskovitz, B. A. Averill, R. H. Holm, J. A. Ibers, W. D. Phillips. and J. F. Weiher, Proc. Natl. Acad. Sci. U.S.A. 69, 2437 (1972).
260
NONHEME METALLOPROTE1NS
[28]
6
o~
2, _ ~~ o
-=
O e..
*6 £
ir
¢-
- . g~3
~
~D
o
h~
rq
e-, ~q
6
L_~ e~
E 6 ._=
o o
~eq t-4
e~ c-
O
g ~eq
[28]
OVERVIEW OF IRON-SULFUR PROTEINS
261
.s cvs
CYS-S~
/'% CYS-S
S-- CYS CA)
CYS-S
.s.
~Fe//"
S-CY$
""" F /
cYs-s/~s~; \s-cYs (B)
~S-CYS
CYS-S ~ . s--:~:~?; F~
i S
i.Ji__
f v ~ Jd" F~ cys--,"s %S-CYS (C) FIG. 2. The recognized types of Fe-S centers found in proteins. Taken from W. H. Orme-Johnson, Annu. Rev. Biochem. 42, 159 (1973).
From the foregoing, and using the abbreviations Rd for rubredoxins (Table I) and Fd for ferredoxins, a nomenclature and shorthand designations for the simple proteins has been devised, 1 as is illustrated in Table III. Note that [Rd] indicates the presence of a single iron atom, [2Fe-2S] and [4Fe-4S] indicate the presence of the 2-Fe and 4-Fe clusters, respectively (Fig. 2), the superscript (or superscripts) indicates the net charge (or range of net charge states normally utilized). A numerical prefix to the brackets indicates the number of clusters present. It is recommended 1 that Fe-S proteins other than the rubredoxins be called ferredoxins and that reference to potential, to denote the range of charge states (as in "high-potential iron-sulfur protein") be dropped, since it appears that the - 1 to - 2 transition can sometimes be associated with rather low potentials, 5 whereas the - 2 to - 3 transition has been found to operate in at least one high-potential electron carrier. 6 Recognition of Fe-S Proteins The presence of iron not bound to heme r and an equivalent amount of acid-labile sulfur 8 is prima facie evidence for the presence of Fe-S W. V. Sweeny, J. C. Rabinowitz, and D. C. Yoch, J. Biol. Chem. 250, 7842 (1975). 0 j. S. Leigh, Jr., and M. Erecifiska, Biochim. Biophys. Acta 387, 95 (1975). 7 p. E. Brumby and V. Massey, this series Vol. 10 [73]. 8 j. C. Rabinowitz, this volume [30].
262
NONHEME METALLOPROTEiNS
[28]
~d
~ =~" ~ x
OVERVIEW OF IRON-SULFUR PROTEINS
259
[28] O v e r v i e w of I r o n - S u l f u r P r o t e i n s B y W. H. ORME-JOHNSON and N. R. ORME-JOHNSON
Definition, N o m e n c l a t u r e , a n d P r o p e r t i e s 1 I r o n - s u l f u r proteins are those in which iron is bound via sulfur-containing ligands. We exclude f r o m consideration hemoproteins, such as c y t o c h r o m e c (and p r e s u m a b l y c y t o c h r o m e P-450), which contain axial sulfur ligands. Figure 1 gives a classification scheme for iron proteins that emphasizes the varieties of Fe-S proteins presently recognized. The group of Fe-S proteins denoted " s i m p l e " , which contain no recognized prosthetic groups other than Fe-S clusters, a p p e a r to function mainly as electron carriers. Useful physical properties of representative m e m b e r s of this group are listed in Table I. The study of this type of protein and a series of synthetic analogs 2 of the iron-sulfur clusters in these proteins led to the conclusion 3 that three types of Fe-S centers in proteins are as depicted in Fig. 2. In addition to the n u m b e r of iron a t o m s present in one of these centers, one needs to specify the oxidation state, which is generally indicated by the net charge state, c o m p u t e d on the assumption that the cysteines are formally present as mercaptide, the labile sulfur as sulfide, and the iron a t o m s as the formally ferric or ferrous state. F o r the k n o w n types of clusters, the oxidation states so far recognized in proteins are shown in Table II. It should be borne in mind that electrochemical studies 2 show that other net charge states of the clusters are possible (although they have not yet been recognized in proteins), and also that there m a y be other types of Fe-S centers in proteins. As shown in Tables I - I I I the high-potential i r o n - s u l f u r proteins and the bacterial-type ferredoxins, each of which contains 4-Fe clusters, differ by which pair of oxidation states are utilized. 4 i Most of the material in this section is adapted from a report (1976) by a subcommittee (H. Beinert, Chairman, R. Cammack, R. H. Holm, L. H. Jensen, J. Kraut, W. Lovenberg, W. H. Orme-Johnson, J. C. Rabinowitz, and E. C. Slater) of the IUPAC--IUB Commission on Biochemical Nomenclature, in which recommendations for the nomenclature of iron-sulfur We-S) proteins are made. Here we give a very brief summary of these recommendations. z R. H. Holm and J. A. lbers, in "Iron-Sulfur Proteins" (W. Lovenberg, ed.), Vol. 3, p. 206. Academic Press, New York, 1977; and references therein. 3 W. H. Orme-Johnson, Annu. Rev. Biochem. 42, 159 (1973); and references therein. 4 T. Herskovitz, B. A. Averill, R. H. Holm, J. A. Ibers, W. D. Phillips. and J. F. Weiher, Proc. Natl. Acad. Sci. U.S.A. 69, 2437 (1972).
260
NONHEME METALLOPROTE1NS
[28]
6
o~
2, _ ~~ o
-=
O e..
*6 £
ir
¢-
- . g~3
~
~D
o
h~
rq
e-, ~q
6
L_~ e~
E 6 ._=
o o
~eq t-4
e~ c-
O
g ~eq
[28]
OVERVIEW OF IRON-SULFUR PROTEINS
261
.s cvs
CYS-S~
/'% CYS-S
S-- CYS CA)
CYS-S
.s.
~Fe//"
S-CY$
""" F /
cYs-s/~s~; \s-cYs (B)
~S-CYS
CYS-S ~ . s--:~:~?; F~
i S
i.Ji__
f v ~ Jd" F~ cys--,"s %S-CYS (C) FIG. 2. The recognized types of Fe-S centers found in proteins. Taken from W. H. Orme-Johnson, Annu. Rev. Biochem. 42, 159 (1973).
From the foregoing, and using the abbreviations Rd for rubredoxins (Table I) and Fd for ferredoxins, a nomenclature and shorthand designations for the simple proteins has been devised, 1 as is illustrated in Table III. Note that [Rd] indicates the presence of a single iron atom, [2Fe-2S] and [4Fe-4S] indicate the presence of the 2-Fe and 4-Fe clusters, respectively (Fig. 2), the superscript (or superscripts) indicates the net charge (or range of net charge states normally utilized). A numerical prefix to the brackets indicates the number of clusters present. It is recommended 1 that Fe-S proteins other than the rubredoxins be called ferredoxins and that reference to potential, to denote the range of charge states (as in "high-potential iron-sulfur protein") be dropped, since it appears that the - 1 to - 2 transition can sometimes be associated with rather low potentials, 5 whereas the - 2 to - 3 transition has been found to operate in at least one high-potential electron carrier. 6 Recognition of Fe-S Proteins The presence of iron not bound to heme r and an equivalent amount of acid-labile sulfur 8 is prima facie evidence for the presence of Fe-S W. V. Sweeny, J. C. Rabinowitz, and D. C. Yoch, J. Biol. Chem. 250, 7842 (1975). 0 j. S. Leigh, Jr., and M. Erecifiska, Biochim. Biophys. Acta 387, 95 (1975). 7 p. E. Brumby and V. Massey, this series Vol. 10 [73]. 8 j. C. Rabinowitz, this volume [30].
262
NONHEME METALLOPROTEiNS
[28]
~d
~ =~" ~ x
