Conformational Analysis of Model Complexes for Methyl‐Coenzyme‐M Reductase from Methanogenic Bacteria: A Comparison of Crystal and Solution Structures

Abstract

In the last step of the archaebacterial methanogenesis, the methylthioether methyl-coenzyme-M 1 reacts with the thiol N-7-mercaptoheptanoyl-0-phospho-L-threonine ("HS-HTP", 2) to yield methane and the mixed disulfide 3. ['] This unusual reaction is brought about by the enzyme methyl-coenzyme-M reductase, which contains the nickel tetrahydrocorphinoid "factor 430" (F430) as cofactor.[21 In general, metalloenzyme-mediated catalysis depends on the specific interaction between substrate(s) and metal ion(s). Also in the case of methyl-coenzyme-M reductase it is assumed that the nickel ion of F430 participates in the catalytic process.131 reductase 3--CH4 + I S -HTP H&. so3 -1 0po32-HO,C"' * H..,, @co2H . N-Ni -N "CH3 -N / ' 7 p ' C 0 2 H -CO2H F430 Transition metal complexes of multidentate ligands have been used successfully as models for the study of metal-substrate interactions in metal lo enzyme^.[^^ For methyl-coenzyme-M reductase, nickel chelates such as rue-4 have been used to simulate the interaction of the organosulfur substrates 1 and 2 with cofactor F430: the comparison of the redox properties of model complexes made it possible to develop a mechanistic hypothesis for the catalytic cycle of methyl-coenzyme-M r e d~c t a s e .~~] The Ni" complexes ruc-4-

1H, 13C, 15N NMR and Theoretical Study of Protonated Carbamic Acids and Related Compounds1

“…The study of their protonated analogues (and their derivatives) is therefore also relevant to a better understanding of protolytic activation of the related biological systems. Recently, Thauer et al have suggested that protosolvolytic activation may play an important role in some enzyme catalytic reactions …”

1H, 13C, 15N NMR and Ab Initio/IGLO/GIAO-MP2 Study of Mono-, Di-, Tri-, and Tetraprotonated Guanidine1

“…For example, a recently discovered metal-free hydrogenase enzyme catalyzes the reversible dehydrogenation of methylenetetrahydromethaneopterin (CH 2 H 4 MPT) to methenyltetrahydromethanopterin (CHH 4 MPT + ) and H 2 . It was suggested that the amidinium ion entity is further activated by N-protonation in the enzyme to bind a H 2 molecule via a two-electron, three-center (2e-3c) bond . The present experimental and theoretical study of protonated guanidines is therefore also relevant to a better understanding of protolytic activation of guanidine containing biological systems.…”

“…In superelectrophilic activation, nonbonded electron pairs on onium ions further interact with Brönsted or Lewis acids and in the limiting case can lead to gitonic dications (polycations), i.e., proximal as contrasted with conventional distonic (distant) dications. In their studies Berkessel and Thauer have suggested that such activation may also play an important role in some enzyme catalytic reactions . For example, a recently discovered metal-free hydrogenase enzyme catalyzes the reversible dehydrogenation of methylenetetrahydromethaneopterin (CH 2 H 4 MPT) to methenyltetrahydromethanopterin (CHH 4 MPT + ) and H 2 .…”

Methyl‐Coenzyme M Reductase and its Nickel Corphin Coenzyme F 430 in Methanogenic Archaea

“…With increasing size the tension in the macrocycle of F 430 decreases and the ring becomes planar, as in high-spin Ni(II)F 430 and Ni(I)F 430 [46]. Different conformations of the ring system and its consequences have also been studied in Ni(II)F 430 model compounds [62,[64][65][66][67][68][69].…”