|
|
| Line 1: |
Line 1: |
| [[Image:1c3v.gif|left|200px]] | | {{Seed}} |
| | [[Image:1c3v.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1c3v| PDB=1c3v | SCENE= }} | | {{STRUCTURE_1c3v| PDB=1c3v | SCENE= }} |
|
| |
|
| '''DIHYDRODIPICOLINATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED WITH NADPH AND PDC'''
| | ===DIHYDRODIPICOLINATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED WITH NADPH AND PDC=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| Dihydrodipicolinate reductase (DHPR) catalyzes the reduced pyridine nucleotide-dependent reduction of the alpha,beta-unsaturated cyclic imine, dihydrodipicolinate, to generate tetrahydrodipicolinate. This enzyme catalyzes the second step in the bacterial biosynthetic pathway that generates meso-diaminopimelate, a component of bacterial cell walls, and the amino acid L-lysine. The Mycobacterium tuberculosis dapB-encoded DHPR has been cloned, expressed, purified, and crystallized in two ternary complexes with NADH or NADPH and the inhibitor 2,6-pyridinedicarboxylate (2,6-PDC). The structures have been solved using molecular replacement strategies, and the DHPR-NADH-2,6-PDC and DHPR-NADPH-2,6-PDC complexes have been refined against data to 2.3 and 2.5 A, respectively. The M. tuberculosis DHPR is a tetramer of identical subunits, with each subunit composed of two domains connected by two flexible hinge regions. The N-terminal domain binds pyridine nucleotide, while the C-terminal domain is involved in both tetramer formation and substrate/inhibitor binding. The M. tuberculosis DHPR uses NADH and NADPH with nearly equal efficiency based on V/K values. To probe the nature of this substrate specificity, we have generated two mutants, K9A and K11A, residues that are close to the 2'-phosphate of NADPH. These two mutants exhibit decreased specificity for NADPH by factors of 6- and 30-fold, respectively, but the K11A mutant exhibits 270% of WT activity using NADH. The highly conserved structure of the nucleotide fold may permit other enzyme's nucleotide specificity to be altered using similar mutagenic strategies.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12962488}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12962488 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_12962488}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 34: |
Line 38: |
| [[Category: Tbsgc]] | | [[Category: Tbsgc]] |
| [[Category: Two-domain structure]] | | [[Category: Two-domain structure]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:17:52 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:10:31 2008'' |
