1n40: Difference between revisions

Revision as of 15:02, 21 February 2008

Atomic structure of CYP121, a mycobacterial P450

OverviewOverview

The first structure of a P450 to an atomic resolution of 1.06 A has been solved for CYP121 from Mycobacterium tuberculosis. A comparison with P450 EryF (CYP107A1) reveals a remarkable overall similarity in fold with major differences residing in active site structural elements. The high resolution obtained allows visualization of several unusual aspects. The heme cofactor is bound in two distinct conformations while being notably kinked in one pyrrole group due to close interaction with the proline residue (Pro(346)) immediately following the heme iron-ligating cysteine (Cys(345)). The active site is remarkably rigid in comparison with the remainder of the structure, notwithstanding the large cavity volume of 1350 A(3). The region immediately surrounding the distal water ligand is remarkable in several aspects. Unlike other bacterial P450s, the I helix shows no deformation, similar to mammalian CYP2C5. In addition, the positively charged Arg(386) is located immediately above the heme plane, dominating the local structure. Putative proton relay pathways from protein surface to heme (converging at Ser(279)) are identified. Most interestingly, the electron density indicates weak binding of a dioxygen molecule to the P450. This structure provides a basis for rational design of putative antimycobacterial agents.

About this StructureAbout this Structure

1N40 is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450., Leys D, Mowat CG, McLean KJ, Richmond A, Chapman SK, Walkinshaw MD, Munro AW, J Biol Chem. 2003 Feb 14;278(7):5141-7. Epub 2002 Nov 14. PMID:12435731

Page seeded by OCA on Thu Feb 21 14:01:59 2008

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OCA

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-[[Image:1n40.gif|left|200px]]<br /><applet load="1n40" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1n40.gif|left|200px]]<br /><applet load="1n40" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1n40, resolution 1.06&Aring;" />
 '''Atomic structure of CYP121, a mycobacterial P450'''<br />
 ==Overview==
-The first structure of a P450 to an atomic resolution of 1.06 A has been, solved for CYP121 from Mycobacterium tuberculosis. A comparison with P450, EryF (CYP107A1) reveals a remarkable overall similarity in fold with major, differences residing in active site structural elements. The high, resolution obtained allows visualization of several unusual aspects. The, heme cofactor is bound in two distinct conformations while being notably, kinked in one pyrrole group due to close interaction with the proline, residue (Pro(346)) immediately following the heme iron-ligating cysteine, (Cys(345)). The active site is remarkably rigid in comparison with the, remainder of the structure, notwithstanding the large cavity volume of, 1350 A(3). The region immediately surrounding the distal water ligand is, remarkable in several aspects. Unlike other bacterial P450s, the I helix, shows no deformation, similar to mammalian CYP2C5. In addition, the, positively charged Arg(386) is located immediately above the heme plane, dominating the local structure. Putative proton relay pathways from, protein surface to heme (converging at Ser(279)) are identified. Most, interestingly, the electron density indicates weak binding of a dioxygen, molecule to the P450. This structure provides a basis for rational design, of putative antimycobacterial agents.
+The first structure of a P450 to an atomic resolution of 1.06 A has been solved for CYP121 from Mycobacterium tuberculosis. A comparison with P450 EryF (CYP107A1) reveals a remarkable overall similarity in fold with major differences residing in active site structural elements. The high resolution obtained allows visualization of several unusual aspects. The heme cofactor is bound in two distinct conformations while being notably kinked in one pyrrole group due to close interaction with the proline residue (Pro(346)) immediately following the heme iron-ligating cysteine (Cys(345)). The active site is remarkably rigid in comparison with the remainder of the structure, notwithstanding the large cavity volume of 1350 A(3). The region immediately surrounding the distal water ligand is remarkable in several aspects. Unlike other bacterial P450s, the I helix shows no deformation, similar to mammalian CYP2C5. In addition, the positively charged Arg(386) is located immediately above the heme plane, dominating the local structure. Putative proton relay pathways from protein surface to heme (converging at Ser(279)) are identified. Most interestingly, the electron density indicates weak binding of a dioxygen molecule to the P450. This structure provides a basis for rational design of putative antimycobacterial agents.
 ==About this Structure==
-N40 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with SO4, HEM and OXY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N40 OCA].
+N40 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=OXY:'>OXY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N40 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Mycobacterium tuberculosis]]
 [[Category: Single protein]]
-[[Category: Chapman, S.K.]]
+[[Category: Chapman, S K.]]
 [[Category: Leys, D.]]
-[[Category: McLean, K.J.]]
+[[Category: McLean, K J.]]
-[[Category: Mowat, C.G.]]
+[[Category: Mowat, C G.]]
-[[Category: Munro, A.W.]]
+[[Category: Munro, A W.]]
 [[Category: Richmond, A.]]
-[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
+[[Category: TBSGC, TB Structural Genomics Consortium.]]
-[[Category: Walkinshaw, M.D.]]
+[[Category: Walkinshaw, M D.]]
 [[Category: HEM]]
 [[Category: OXY]]
@@ Line 33: / Line 33: @@
 [[Category: tbsgc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:56:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:01:59 2008''