2h2a
From Proteopedia
(New page: 200px<br /><applet load="2h2a" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h2a, resolution 2.10Å" /> '''Crystal structure of...) |
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| - | [[Image:2h2a.gif|left|200px]]<br /><applet load="2h2a" size=" | + | [[Image:2h2a.gif|left|200px]]<br /><applet load="2h2a" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2h2a, resolution 2.10Å" /> | caption="2h2a, resolution 2.10Å" /> | ||
'''Crystal structure of Nicotinic acid mononucleotide adenylyltransferase from Staphylococcus aureus: product bound form 2'''<br /> | '''Crystal structure of Nicotinic acid mononucleotide adenylyltransferase from Staphylococcus aureus: product bound form 2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Bacterial nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC | + | Bacterial nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) encoded by the nadD gene, is essential for cell survival and is thus an attractive target for developing new antibacterial agents. The NaMNAT catalyzes the transfer of an adenylyl group of ATP to nicotinic acid mononucleotide (NaMN) to form nicotinic acid dinucleotide (NaAD). Two independently derived, high-resolution structures of Staphylococcus aureus NaMNAT-NaAD complexes establish the conserved features of the core dinucleotide-binding fold with other adenylyltransferases from bacteria to human despite a limited sequence conservation. The crystal structures reveal that the nicotinate carboxylates of NaAD are recognized by interaction with the main-chain amides of Thr85 and Tyr117, a positive helix dipole and two bridged-water molecules. Unlike other bacterial adenylyltransferases, where a partially conserved histidine residue interacts with the nicotinate ring, the Leu44 side-chain interacts with the nicotinate ring by van der Waals contact. Importantly, the S. aureus NaMNAT represents a distinct adenylyltransferase subfamily identifiable in part by common features of dimerization and substrate recognition in the loop connecting beta5 to beta6 (residues 132-146) and the additional beta6 strand. The unique beta6 strand helps orient the residues in the loop connecting beta5 to beta6 for substrate/product recognition and allows the beta7 strand structural flexibility to make key dimer interface interactions. Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for S. aureus NaMNAT and for rational design of selective inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 2H2A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with CA, DND and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide_adenylyltransferase Nicotinate-nucleotide adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.18 2.7.7.18] Full crystallographic information is available from [http:// | + | 2H2A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=DND:'>DND</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide_adenylyltransferase Nicotinate-nucleotide adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.18 2.7.7.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H2A OCA]. |
==Reference== | ==Reference== | ||
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[[Category: nmnat]] | [[Category: nmnat]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:27 2008'' |
Revision as of 15:37, 21 February 2008
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Crystal structure of Nicotinic acid mononucleotide adenylyltransferase from Staphylococcus aureus: product bound form 2
Overview
Bacterial nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) encoded by the nadD gene, is essential for cell survival and is thus an attractive target for developing new antibacterial agents. The NaMNAT catalyzes the transfer of an adenylyl group of ATP to nicotinic acid mononucleotide (NaMN) to form nicotinic acid dinucleotide (NaAD). Two independently derived, high-resolution structures of Staphylococcus aureus NaMNAT-NaAD complexes establish the conserved features of the core dinucleotide-binding fold with other adenylyltransferases from bacteria to human despite a limited sequence conservation. The crystal structures reveal that the nicotinate carboxylates of NaAD are recognized by interaction with the main-chain amides of Thr85 and Tyr117, a positive helix dipole and two bridged-water molecules. Unlike other bacterial adenylyltransferases, where a partially conserved histidine residue interacts with the nicotinate ring, the Leu44 side-chain interacts with the nicotinate ring by van der Waals contact. Importantly, the S. aureus NaMNAT represents a distinct adenylyltransferase subfamily identifiable in part by common features of dimerization and substrate recognition in the loop connecting beta5 to beta6 (residues 132-146) and the additional beta6 strand. The unique beta6 strand helps orient the residues in the loop connecting beta5 to beta6 for substrate/product recognition and allows the beta7 strand structural flexibility to make key dimer interface interactions. Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for S. aureus NaMNAT and for rational design of selective inhibitors.
About this Structure
2H2A is a Single protein structure of sequence from Staphylococcus aureus with , and as ligands. Active as Nicotinate-nucleotide adenylyltransferase, with EC number 2.7.7.18 Full crystallographic information is available from OCA.
Reference
Crystal structure of nicotinic acid mononucleotide adenylyltransferase from Staphyloccocus aureus: structural basis for NaAD interaction in functional dimer., Han S, Forman MD, Loulakis P, Rosner MH, Xie Z, Wang H, Danley DE, Yuan W, Schafer J, Xu Z, J Mol Biol. 2006 Jul 21;360(4):814-25. Epub 2006 Jun 6. PMID:16784754
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Categories: Nicotinate-nucleotide adenylyltransferase | Single protein | Staphylococcus aureus | Han, S. | CA | DND | GOL | Nadd | Namnat | Nmnat
