Crystal structure of substrate complexes of methylmalonyl-CoA mutase

被引:107
作者
Mancia, F
Smith, GA
Evans, PR
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England
关键词
D O I
10.1021/bi9903852
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
X-ray crystal structures of methylmalonyl-CoA mutase in complexes with substrate methylmalonyl-CoA and inhibitors 2-carboxypropyl-CoA and 3-carboxypropyl-CoA (substrate and product analogues) show that the enzyme-substrate interactions change little during the course of the rearrangement reaction, in contrast to the large conformational change on substrate binding. The substrate complex shows a 5'-deoxyadenine molecule in the active site, bound weakly and not attached to the cobalt atom of coenzyme B-12, rotated and shifted from its position in the substrate-free adenosylcobalamin complex. The position of Tyr alpha 89 close to the substrate explains the stereochemical selectivity of the enzyme for (2R)-methylmalonyl-CoA.
引用
收藏
页码:7999 / 8005
页数:7
相关论文
共 21 条
[11]   Tritium isotope effects in adenosylcobalamin-dependent methylmalonyl-CoA mutase [J].
Meier, TW ;
Thoma, NH ;
Leadlay, PF .
BIOCHEMISTRY, 1996, 35 (36) :11791-11796
[12]   Refinement of macromolecular structures by the maximum-likelihood method [J].
Murshudov, GN ;
Vagin, AA ;
Dodson, EJ .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 1997, 53 :240-255
[13]   AMORE - AN AUTOMATED PACKAGE FOR MOLECULAR REPLACEMENT [J].
NAVAZA, J .
ACTA CRYSTALLOGRAPHICA SECTION A, 1994, 50 :157-163
[14]   Evidence that cobalt-carbon bond homolysis is coupled to hydrogen atom abstraction from substrate in methylmalonyl-CoA mutase [J].
Padmakumar, R ;
Padmakumar, R ;
Banerjee, R .
BIOCHEMISTRY, 1997, 36 (12) :3713-3718
[15]   COENZYME B-12 IS COORDINATED BY HISTIDINE AND NOT DIMETHYLBENZIMIDAZOLE ON METHYLMALONYL-COA MUTASE [J].
PADMAKUMAR, R ;
TAOKA, S ;
PADMAKUMAR, R ;
BANERJEE, R .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (26) :7033-7034
[16]   STEREOCHEMISTRY OF COENZYME-B12-DEPENDENT METHYLMALONYL-COA-MUTASE REACTION - INVESTIGATION WITH ETHYLMALONYL-COA [J].
RETEY, J ;
ZAGALAK, B .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1973, 12 (08) :671-672
[17]  
THOMA N, 1999, THESIS U CAMBRIDGE
[18]   Stabilization of radical intermediates by an active-site tyrosine residue in methylmalonyl-CoA mutase [J].
Thomä, NH ;
Meier, TW ;
Evans, PR ;
Leadlay, PF .
BIOCHEMISTRY, 1998, 37 (41) :14386-14393
[19]   ON THE MECHANISM OF ACTION OF METHYLMALONYL-COA MUTASE - CHANGE OF THE STERIC COURSE ON ISOTOPE SUBSTITUTION [J].
WOLFLE, K ;
MICHENFELDER, M ;
KONIG, A ;
HULL, WE ;
RETEY, J .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1986, 156 (03) :545-554
[20]   Cloning, sequencing, expression, and insertional inactivation of the gene for the large subunit of the coenzyme B12-dependent isobutyryl-CoA mutase from Streptomyces cinnamonensis [J].
Zerbe-Burkhardt, K ;
Ratnatilleke, A ;
Philippon, N ;
Birch, A ;
Leiser, A ;
Vrijbloed, JW ;
Hess, D ;
Hunziker, P ;
Robinson, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (11) :6508-6517