Crystal structure of the catalytic domain of the PknB serine/threonine kinase from Mycobacterium tuberculosis

被引:137
作者
Ortiz-Lombardía, M [1 ]
Pompeo, F [1 ]
Boitel, B [1 ]
Alzari, PM [1 ]
机构
[1] Inst Pasteur, Unite Biochim Struct, URA 2185 CNRS, F-75724 Paris 15, France
关键词
D O I
10.1074/jbc.M300660200
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
With the advent of the sequencing programs of prokaryotic genomes, many examples of the presence of serine/threonine protein kinases in these organisms have been identified. Moreover, these kinases could be classified as homologues of those belonging to the well characterized superfamily of the eukaryotic serine/threonine and tyrosine kinases. Eleven such kinases were recognized in the genome of Mycobacterium tuberculosis. Here we report the crystal structure of an active form of PknB, one of the four M. tuberculosis kinases that are conserved in the downsized genome of Mycobacterium leprae and are therefore presumed to play an important role in the processes that regulate the complex life cycle of mycobacteria. Our structure confirms again the extraordinary conservation of the protein kinase fold and constitutes a landmark that extends this conservation across the evolutionary distance between high eukaryotes and eubacteria. The structure of PknB, in complex with a nucleotide triphosphate analog, reveals an enzyme in the active state with an unprecedented arrangement of the Gly-rich loop associated with a new conformation of the nucleotide gamma-phosphoryl group. It presents as well a partially disordered activation loop, suggesting an induced fit mode of binding for the so far unknown substrates of this kinase or for some modulating factor(s).
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页码:13094 / 13100
页数:7
相关论文
共 38 条
[31]   2 STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHORYLASE-KINASE - AN ACTIVE PROTEIN-KINASE COMPLEXED WITH SUBSTRATE-ANALOG AND PRODUCT [J].
OWEN, DJ ;
NOBLE, MEM ;
GARMAN, EF ;
PAPAGEORGIOU, AC ;
JOHNSON, LN .
STRUCTURE, 1995, 3 (05) :467-482
[32]   A serine/threonine protein kinase from Mycobacterium tuberculosis [J].
Peirs, P ;
DeWit, L ;
Braibant, M ;
Huygen, K ;
Content, J .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 244 (02) :604-612
[33]   PROTEIN-KINASES .8. HOW DO PROTEIN-KINASES DISCRIMINATE BETWEEN SERINE THREONINE AND TYROSINE - STRUCTURAL INSIGHTS FROM THE INSULIN-RECEPTOR PROTEIN-TYROSINE KINASE [J].
TAYLOR, SS ;
RADZIOANDZELM, E ;
HUNTER, T .
FASEB JOURNAL, 1995, 9 (13) :1255-1266
[34]   Catalytic subunit of cyclic AMP-dependent protein kinase: Structure and dynamics of the active site cleft [J].
Taylor, SS ;
Radzio-Andzelm, E ;
Madhusudan ;
Cheng, XD ;
Eyck, LT ;
Narayana, N .
PHARMACOLOGY & THERAPEUTICS, 1999, 82 (2-3) :133-141
[35]   Crystallographic and solution studies of an activation loop mutant of the insulin receptor tyrosine kinase - Insights into kinase mechanism [J].
Till, JH ;
Ablooglu, AJ ;
Frankel, M ;
Bishop, SM ;
Kohanski, RA ;
Hubbard, SR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :10049-10055
[36]  
WANG JYJ, 1978, J BIOL CHEM, V253, P7605
[37]   CRYSTAL-STRUCTURE OF THE CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE COMPLEXED WITH MGATP AND PEPTIDE INHIBITOR [J].
ZHENG, JH ;
KNIGHTON, DR ;
TENEYCK, LF ;
KARLSSON, R ;
XUONG, NH ;
TAYLOR, SS ;
SOWADSKI, JM .
BIOCHEMISTRY, 1993, 32 (09) :2154-2161
[38]   Is there a catalytic base in the active site of cAMP-dependent protein kinase? [J].
Zhou, J ;
Adams, JA .
BIOCHEMISTRY, 1997, 36 (10) :2977-2984