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5d6n

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Crystal structure of a mycobacterial protein

Structural highlights

5d6n is a 1 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.401Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FAA32_MYCS2 Involved in the biosynthesis of mycolic acids (By similarity). Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the phosphopantetheine arm of the polyketide synthase Pks13 for further chain extension (By similarity). Can use decanoate (C10), dodecanoate (C12) and tetradecanoate (C14) (PubMed:23364516, PubMed:26900152).[UniProtKB:O53580]^[1] ^[2]

Publication Abstract from PubMed

Fatty acid degradation protein D32 (FadD32), an enzyme required for mycolic acid biosynthesis and essential for mycobacterial growth, has recently been identified as a valid and promising target for anti-tuberculosis drug development. Here we report the crystal structures of Mycobacterium smegmatis FadD32 in the apo and ATP-bound states at 2.4 A and 2.25 A resolution, respectively. FadD32 consists of two globular domains connected by a flexible linker. ATP binds in a cleft at the interface between the N- and C-terminal domains and its binding induces significant local conformational changes in FadD32. The binding sites of meromycolic acid and phosphopantetheine are identified by structural comparison with other members of the adenylating enzyme superfamily. These results will improve our understanding of the catalytic mechanism of FadD32 and help in the design of inhibitors of this essential enzyme.

Crystal structure of FadD32, an enzyme essential for mycolic acid biosynthesis in mycobacteria.,Li W, Gu S, Fleming J, Bi L Sci Rep. 2015 Dec 2;5:15493. doi: 10.1038/srep15493. PMID:26628098^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Galandrin S, Guillet V, Rane RS, Léger M, N R, Eynard N, Das K, Balganesh TS, Mourey L, Daffé M, Marrakchi H. Assay development for identifying inhibitors of the mycobacterial FadD32 activity. J Biomol Screen. 2013 Jun;18(5):576-87. PMID:23364516 doi:10.1177/1087057112474691
↑ Guillet V, Galandrin S, Maveyraud L, Ladeveze S, Mariaule V, Bon C, Eynard N, Daffe M, Marrakchi H, Mourey L. Insight into Structure-Function Relationships and Inhibition of the Fatty Acyl-AMP Ligase (FadD32) Orthologs from Mycobacteria. J Biol Chem. 2016 Apr 8;291(15):7973-89. doi: 10.1074/jbc.M115.712612. Epub 2016 , Feb 21. PMID:26900152 doi:http://dx.doi.org/10.1074/jbc.M115.712612
↑ Li W, Gu S, Fleming J, Bi L. Crystal structure of FadD32, an enzyme essential for mycolic acid biosynthesis in mycobacteria. Sci Rep. 2015 Dec 2;5:15493. doi: 10.1038/srep15493. PMID:26628098 doi:http://dx.doi.org/10.1038/srep15493