Manisha Gupta

The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21.

Human cytochrome P450c17 (17alpha-hydroxylase, 17,20-lyase) (CYP17) and cytochrome P450c21 (21-hydroxylase) (CYP21) differ by only 14 amino acids in length and share 29% amino acid identity. Both enzymes hydroxylate progesterone at carbon atoms that lie only 2.6A apart, but CYP17 also metabolizes other steroids and demonstrates additional catalytic activities. To probe the active site topologies of these related enzymes, we synthesized the enantiomer of progesterone and determined if ent-progesterone is a substrate or inhibitor of CYP17 and CYP21. Neither enzyme metabolizes ent-progesterone; however, ent-progesterone is a potent competitive inhibitor of CYP17 (K(I)=0.2 microM). The ent-progesterone forms a type I difference spectrum with CYP17, but molecular dynamics simulations suggest different binding orientations for progesterone and its enantiomer. The ent-progesterone also inhibits CYP21, with weaker affinity than for CYP17. We conclude that CYP17 accommodates the stereochemically unnatural ent-progesterone better than CYP21. Enantiomeric steroids can be used to probe steroid binding sites, and these compounds may be effective inhibitors of steroid biosynthesis.

Why human cytochrome P450c21 is a progesterone 21-hydroxylase

Human cytochrome P450c21 (steroid 21-hydroxylase, CYP21A2) catalyzes the 21-hydroxylation of progesterone (P4) and its preferred substrate 17α-hydroxyprogestrone (17OHP4). CYP21A2 activities, which are required for cortisol and aldosterone biosynthesis, involve the formation of energetically disfavored primary carbon radicals. Therefore, we hypothesized that the binding of P4 and 17OHP4 to CYP21A2 restricts access of the reactive heme-oxygen complex to the C-21 hydrogen atoms, suppressing oxygenation at kinetically more favorable sites such as C-17 and C-16, which are both hydroxylated by cytochrome P450c17 (CYP17A1). We reasoned that expansion of the CYP21A2 substrate-binding pocket would increase substrate mobility and might yield additional hydroxylation activities. We built a computer model of CYP21A2 based principally on the crystal structure of CYP2C5, which also 21-hydroxylates P4. Molecular dynamics simulations indicate that binding of the steroid nucleus perpendicular to the plane of the CYP21A2 heme ring limits access of the heme oxygen to the C-21 hydrogen atoms. Residues L107, L109, V470, I471, and V359 were found to contribute to the CYP21A2 substate-binding pocket. Mutation of V470 and I471 to alanine or glycine preserved P4 21-hydroxylase activity, and mutations of L107 or L109 were inactive. Mutations V359A and V359G, in contrast, acquired 16α-hydroxylase activity, accounting for 40% and 90% of the P4 metabolites, respectively. We conclude that P4 binds to CYP21A2 in a fundamentally different orientation than to CYP17A1 and that expansion of the CYP21A2 substrate-binding pocket allows additional substrate trajectories and metabolic switching.

Towards a unifying mechanism for CYP17 mutations that cause isolated 17, 20-lyase deficiency

Cytochrome P450c17 (CYP17) is a single hemoprotein that catalyzes both the 17α-hydroxylase and 17, 20-lyase reactions in all species thus far examined. Severe defects in CYP17 cause classical 17-hydroxylase deficiency, but other defects result in partial or selective deficiency states. One such variant is the syndrome of isolated 17, 20-lyase deficiency. Recent detailed studies of the biochemical properties of the mutant CYP17 enzymes from patients with isolated 17, 20-lyase deficiency demonstrate that alterations in the interaction of CYP17 with its redox partner proteins P450-oxidoreductase and cytochrome b5 form the biochemical basis for these selective enzyme defects. Site-directed mutagenesis studies have confirmed that neutralization of any of several positive charges on the redox partner binding surface results in selective disruption of 17, 20-lyase activity. In one case diagnosed as isolated 17, 20-lyase deficiency, the identified mutation did not map to the redox partner binding surface; however, we have shown that this mutation cannot be the cause of isolated 17, 20-lyase deficiency in this patient. These consistent results have prompted us to propose a paradigm in which neutralization of positive charges in the redox partner binding surface of CYP17 may be the predominant if not sole mechanism leading to isolated 17, 20-lyase deficiency.

Design and Evaluation of BER for Ultra-Wide-Band System for Different Modulation Schemes

It’s already been 40 years of the development of Ultra-Wide-Band System but still it is one of the most promising technology for physical layer i.e. short range wireless communication due to its advantages of multipath fading immunity, low power spectral density, capability of generating a maximum data rate etc. This technology have a capability to send out the data at the rate of 100 Mbps which can be further increased by using a high order modulation scheme. From the result it is also analyzed that Inter-Symbol-Interference is one of the biggest hurdle in UWB System, so to overcome this problem, the efficient receiver and transmitter has to be design. In the proposed work, the UWB is designed for Line of Sight (LOS) and Non-Line of Sight (N-LOS) 802.15.3a channel for three modulation schemes i.e. BPSK, QPSK and QAM and Bit-Error-Rate is also calculated for these modulation schemes. On the basis of Bit-Error-Rate and other simulated results it is concluded that BPSK is most robust and best modulation scheme for Ultra-Wide-Band System.

Design of 4:8 MIMO OFDM with MSE Equalizer for Different Modulation Techniques

MIMO OFDM is one of the most promising techniques to increase the capacity and data rate in mobile communication. In this work MIMO-OFDM is designed by using 4:8 antenna and OSTBC encoder and combiner for different modulation techniques like BPSK, QPSK, QAM-16, QAM-64, QAM-256 and MSE equalizer is also used which further reduce the inter-symbol interference specially for high order modulation techniques and enhanced the performance of OFDM system. Simulation is performed to analyze the performance of different modulation technique on the basis of BER, SNR, MSE plot, constellation plot etc. It is also found that for OFDM, the BER of QPSK is 0 and QAM-16, QAM-64 and QAM-256 have almost same BER but reduction in ISI also achieved.

Design of Compact Triangular Patch Antenna for WiMax Applications

This paper presents a design of triangular microstrip patch antenna with varying substrate heights. The operating frequency used is in the range 1–3 GHz for wireless communication systems. Microstrip patch antenna with triangular shape is fabricated on FR-4 substrate which has a relative permittivity of 4.4 and mounted at a height above ground plane. Important parameters of antenna like return loss, input impedance, antenna gain, and VSWR are observed and comparison is done among the different antenna widths.

Hexagonal Fractal Antenna using Koch for Wireless Applications

Abstract This paper presents the design, fabrication, and measurement of a novel ultra-wideband (UWB) hexagonal fractal patch antenna. This antenna uses hexagonal shape with Koch snowflake fractal at its edges. The proposed antenna has been excited using microstrip feed. The measured result of this antenna offers the ultra wideband characteristics from 3.265 GHz to 8.2 GHz. The antenna is practically fabricated and tested. Measured results show a good agreement with simulated results. The measured radiation patterns of this antenna are nearly omnidirectional in H-plane and bidirectional in E-plane. This antenna holds applications in many satellite communication transmissions, some Wi-Fi devices, cordless telephones, and weather radar systems. In this paper, an approach for multi-band antennas is proposed. First, a hexagonal patch is taken, it is fractured using Koch structure. The antenna shows compact dimensions with good S11 and pattern performance to be adopted for UWB applications.

Design, Analysis of 4×4 and 8×8 MIMO System with ZF, MMSE and BF Techniques

Abstract This work focuses on studying signal detection using three different equalization techniques, namely: Zero Forcing (ZF), Minimum Mean Square Error (MMSE) and Beam Forming (BF), for a 4×4 MIMO-system. Results show that ZF equalization is the simplest technique for signal detection, However, Beam Forming (BF) gives better Bit Error Rate (BER) performances at high Signal to Noise Ratio (SNR) values with some complexity in design. For more antennas at the base station, it is too complex to design the weight matrix for ZF, however, it is suitable for BF with the help of good quality digital signal processors. Performance of MIMO-system, with 8 antennas at the base station using BF equalization, is analysed to get BER values at different SNR. Results show a considerable improvement in BER for 8 antennas at the base station.

Dual Band Microstrip Antenna using Shorted Metallic Patches

A compact monopole antenna having dual band characteristics using shorted metallic patches is presented. To get impedance matching for the SMA conductor, the antenna is fed up by probe feeding technique. The shorted metallic patches are made by square patches which are connected to the ground plane by the shorting pins. SMPs are used to improve the gain of the antenna. The dimensions and position of the SMPs and the position and dimension of the slot with respect to the patch are important and studied in this paper.

Design, Development of MC-CDMA, and Reduction of ISI for Different Modulation Techniques

With the increasing demand of high data rate and increased in capacity, it is become necessary to analyze thedifferent modulating techniques. By using a good modulation schemes, the growth in speed and capacity can be achieved. In thispaper, we have designed a MC-CDMA for different modulation methods like BPSK, QPSK, 256-QAM, 512-QAM and 1024-QAM.To reduce the Inter-Symbol-Interference, MSE Equalization technique is used. Result shows the plot of Signal to Noise RatioVsEb/No and MMSE Vs SNR which clearly shows the performance improvement in MC-CDMA as compared to anyexisted MC-CDMA system for proposed modulation techniques.